Serbian superstar Djokovic scraped past Stefanos Tsitsipas in their semi-final on Saturday, snatching a 6-2 3-6 7-6 (7-4) victory.
Now 19-year-old Danish player Rune awaits the 21-time grand slam winner in Sunday's title match, a clash of generations that is full of promise.
It will be a record 56th Masters 1000 final for Djokovic, and a first for Rune, who will climb to 10th in the world should he win.
Rune is already assured of at least 12th position on the ATP list, a career-high, after knocking out four top-10 players this week: Hubert Hurkacz, Andrey Rublev, Carlos Alcaraz – who retired when trailing in their quarter-final – and Felix Auger-Aliassime, who he beat 6-4 6-2 on Saturday.
In his entire young career before this week, Rune had only beaten four players from the top 10, so this week marks a significant step, no matter how the final goes.
"No doubt that he's the future of the sport, along with Alcaraz and some other guys," Djokovic said. "Hopefully I can suspend his first title Masters 1000 event. We get along really well, good friends off the court.
"Of course on the court, we're competitors. I played him only once, at the last US Open, a good battle, four sets. He has improved a lot, no doubt. He physically is a very fit guy. He's young, so not much to lose. Just swinging through the ball.
"He kind of reminds me of myself, solid backhand and very good defence and just competitive, every point leaving his heart and his legs out there on the court. It's nice to see that. I think he's very good for our sport in general."
Djokovic said it was reassuring to fend off Tsitsipas, who had led by a break in the deciding tie-break.
"It means a lot mentally, emotionally for me, more than anything," said Djokovic. "I need to also make a statement that I'm still there with the young guys, that I'm able to compete with them and win such tight matches."
Six-time champion Djokovic has now reached an eighth final at this tournament, getting to the title match three times more than anyone else, with Boris Becker next on the list with five appearances.
Djokovic had not featured in an ATP-level match since his final victory over Nick Kyrgios at Wimbledon, having been forced to miss the US Open due to his COVID-19 vaccination status.
But the Serbian needed little time to find his feet in Israel, winning the first seven games of the match and breaking the Spaniard's serve four times en route to a 6-0 6-3 victory.
Speaking on court afterwards, Djokovic said: "Fantastic atmosphere here tonight, thank you very much. I like the court, it's very intimate and it's very loud.
"The crowd here is very passionate about the sport, about tennis and I'm really, really happy to be here and to perform here in front of you, so thank you for your support."
The 21-time grand slam winner will face Canada's Vasek Pospisil in the last eight after he beat home hopeful Edan Leshem 6-3 6-2.
Two of Djokovic's fellow seeds fared less well, however, with Diego Schwartzman and Botic van de Zandschulp both being ousted after three-set contests.
Third seed Schwartzman failed to capitalise on a third-set match point in his 6-3 2-6 7-6 (9-7) loss to Arthur Rinderknech, while Britain's Liam Broady teed up a clash with Marin Cilic by beating Van de Zandschulp 6-4 4-6 6-3.
The Sofia Open also saw a couple of seeds fall to surprise defeats on Thursday, although Jannik Sinner avoided any drama in his 6-3 6-4 win over Nuno Borges.
Sinner now has a perfect 10-0 record at the event, which he won in both 2020 and 2021, and will face Australia's Aleksandar Vukic for a place in the final four.
Holger Rune also progressed to the last eight, though he was forced to rally after losing the opener against Lorenzo Sonego, but Pablo Carreno Busta and Oscar Otte were both dumped out.
Second seed Carreno Busta fell to a 6-3 3-6 6-2 reverse against Switzerland's Marc-Andrea Huesler, who will face Poland's Kamil Majchrzak in the quarter-finals after he came back to beat Otte 4-6 6-2 6-4.
Djokovic's 12-match winning run looked likely to be halted when Tsitsipas found a mini-break in the decider, with the Greek having fought his way into contention after losing the opening set.
However, the 21-time grand slam champion stepped up when it mattered, winning the final four points of the match to seal a 6-2 3-6 7-6 (7-4) victory.
The Serbian, who will now take part in his record 56th Masters 1000 final on Sunday, opted to praise Tsitsipas for his role in a thrilling encounter following the win.
"It's very sweet, obviously, when you win matches like this against one of the best players in the world," Djokovic said.
"I thought I started the match very well, again, great hitting, like yesterday in the quarters. I had chances early on in the second, I didn't break his serve. The momentum shifted, the crowd got into it. I think he elevated his level of tennis.
"We went into an even battle all the way until the last point, until the last shot. Some incredible points towards the end. I'm just really glad to overcome this challenge."
In Saturday's other match, Rune clinched his first Masters 1000 final appearance by posting a straight-sets victory over Felix Auger-Aliassime.
The in-form Dane seized control of the contest after breaking in the third game of the opener, and did not give up a single break point en route to a comprehensive 6-4 6-2 win.
In doing so, Rune exacted revenge for last week's defeat to Auger-Aliassime in the Swiss Indoors final in Basel, halting the Canadian's 16-match winning run.
Rune has now won eight career matches against top-10 opponents, and half of those victories (four) have come during his strong run in Paris this week.
Twenty-four time grand slam winner Djokovic added another Australian Open, French Open and US Open crown to his collection this year.
The 36-year-old won a Tour-best seven singles titles in 2023 and finished top of the ATP Rankings for a record-extending eighth year in a row.
"I think it's great to see that Novak can still play at this level. It's unbelievable what he's doing," Rune said.
Only Carlos Alcaraz stopped Djokovic from landing a career first calendar Grand Slam with his triumph in the Wimbledon final.
However, if the next generation are to truly take the mantle from Djokovic, Rune accepts they need to start bloodying the Serbian's nose more regularly.
Alcaraz was closest to Djokovic in 2023 with six tour titles, while Daniil Medvedev won five and Jannik Sinner four.
For all the talk of someone new potentially dominating the male game, though, Rune does not believe Djokovic's era of dominance is over yet.
"Alcaraz won a slam this year. Sinner finished in the top four. I was number four for the first time this year," he said.
"I think the next generation is very interesting. I think we are trying to compete with Novak and to see if we can match him.
"Still, he's winning three out of four grand slams - it's kind of tough. Before we can say that, we need to start winning more regularly against him."
The Serbian was made to work hard by his Canadian opponent, particularly in the first set, but eventually won 7-6 (7-5) 6-3.
Djokovic was particularly impressive on his second serve, winning 70 per cent of them, only four per cent less than his first serve success rate, and he hit just eight unforced errors compared to Pospisil's 21.
"It was a great, positive win," Djokovic said afterwards. "Vasek is one of my best friends on the Tour. We have known each other for many years. It is never easy playing someone you respect so much and like so much, but we are both professionals and wanted to win the match and you can see that.
"I think the level of tennis was really high. Especially towards the end of the first set and the second set. Credit to him for fighting. It's great to see him back."
The number one seed will play Roman Safiullin in the semi-finals after the Russian beat Arthur Rinderknech 6-4 6-1.
Constant Lestienne came through a tight contest with Maxime Cressy, winning 6-7 (4-7) 6-3 7-6 (7-3), and will face number two seed Marin Cilic in the other semi after the Croatian was handed a bye following Liam Broady's withdrawal prior to their match.
At the Sofia Open, Jannik Sinner remains on course for a third successive title at the tournament, setting up a final-four encounter with Holger Rune after easing past Aleksandar Vukic 6-2 6-3, with Rune eventually dispatching Ilya Ivashka 6-2 5-7 6-4.
The other semi-final in Bulgaria will see Lorenzo Musetti take on Marc-Andrea Huesler after both won their respective quarter-finals against Jan-Lennard Struff and Kamil Majchrzak.
Djokovic moved into the last four of a Masters 1000 event for a staggering 74th time with a commanding 6-0 6-3 victory over Musetti on Friday.
The defending champion will do battle with Stefanos Tsitsipas for a place in the final as he eyes a seventh Paris Masters title.
Sixth seed Djokovic made only 10 unforced errors and broke five times, not allowing his Italian opponent to have a game point until early in the second set.
The 21-time grand slam champion only needed 74 minutes to dispatch the unseeded Musetti, moving two victories away from a fifth title of the season.
Meanwhile, world number one Alcaraz's participation in the ATP Finals next week is in doubt after he was injured in his quarter-final against Holger Rune.
Rune won the first set 6-3 and the Dane was 3-1 up in a second-set tie-break when US Open champion Alcaraz brought the match to a premature end.
As Alcaraz prepares to discover whether he can play in the season-ending tournament in Turin, Rune can look forward to facing Felix Auger-Aliassime in his maiden Masters 1000 semi-final.
Auger-Aliassime beat Rune to take the title in Basel last weekend and the Canadian stretched his winning run to 16 matches by beating Frances Tiafoe 6-1 6-4.
Tsitsipas was the last man to seal his place in the semi-finals, getting the better of Tommy Paul, who beat Rafael Nadal earlier in the week, 6-2 6-4.
Fritz was among the seeds to progress, alongside Casper Ruud, Holger Rune, Francis Tiafoe and Tommy Paul.
The third seed lost the opening set in 29 minutes but rallied back to win 3-6 6-3 6-4 in one hour and 49 minutes over the big-serving world number 38 Isner.
Fritz claimed his first break of the match in the 17th game before levelling things up at one set each, before breaking Isner at 4-4 in the third and serving out for victory.
The win means Fritz will take on Canada's Denis Shapovalov in the second round after he beat Miomir Kecmanovic in three sets, with the American looking to go one better after being runner-up in Acapulco in 2020.
Second seed Ruud found himself in an almighty battle with Argentina's Guido Andreozzi and eventually prevailed 6-4 4-6 7-6 (7-2).
World number four Ruud, ranked 338 places above his opponent, was broken in the first game of each set but dug deep to get the job done in a little under three hours.
Fourth seed Rune got past 2023 Australian Open quarter-finalist Ben Shelton 6-7 (7-9) 6-4 6-2.
Sixth seed Tiafoe overcame Japan's Yoshihito Nishioka 7-6 (8-6) 6-4 while 2023 Australian Open semi-finalist Paul beat Emilio Gomez 6-1 7-6 (7-4).
Defending champion Pedro Martinez was bundled out of the Chile Open in the first round after losing 6-2 6-0 to German qualifier Yannick Hanfmann.
Jaume Munar progressed to set up a second-round clash with top seed Lorenzo Musetti after winning 6-0 6-7 (4-7) 7-6 (7-5) against Alejandro Tabilo.
Rune reached Sunday's decider with a semi-final triumph over top seed Jannik Sinner, who was bidding to win three straight titles in Sofia.
But it was Husler who took the first set, breaking his Danish opponent in the first game of the match before holding in all five of his service games to clinch the opener.
The second set was another tight affair, as both players continued to dominate on their serve. However, the match hit a crucial juncture with Rune leading the second set 6-5, as he spurned two set points to break Husler and level the final up.
Husler survived to take the second set to a tie-break, though Rune again had the opportunity to make it one set apiece as he failed to convert another two set points in the tie-break.
And Husler took advantage with two crucial breaks of Rune's serve to seal the victory and become the first Swiss player to win an ATP Tour title since Roger Federer in 2019.
"I am completely taken aback," Husler said in his on-court interview.
"I am lost for words. It was a great match. I played a great, great match for sure. I just tried to stay focused, stayed calm and I am just really happy I was able to make it."
Huesler arrived in Montpellier on a high from victories over German duo Alexander Zverev and Oscar Otte for Switzerland in Davis Cup qualifiers last weekend.
The left-hander saw off 18-year-old Frenchman Van Assche 6-3 3-6 6-3 and will get a chance to improve his perfect record against Rune to 3-0.
Italian Lorenzo Sonego sent eighth seed Benjamin Bonzi packing with a 6-4 6-3 win, while French-born American Maxime Cressy progressed with a 6-3 6-2 defeat of Antoine Bellier.
Arthur Rinderknech and Quentin Halys also advanced on home soil, along with Marton Fucsovics and Filip Krajinovic.
Rune was beaten by Marc-Andrea Huesler in the final of the last tournament he entered in Sofia following a quarter-final appearance in Metz.
The Danish teenager, who last week announced Patrick Mouratoglou had joined his team for the rest of this season, defeated Monteiro 7-5 6-2 on his debut in the Swedish capital.
Rune did not face a break point and won 86 per cent of points on his first serve as he booked a meeting with Cristian Garin.
Garin beat qualifier Jason Kubler 6-2 6-4, while Maxime Cressy and Aslan Karatsev advanced to the last 16 at the expense of Ilya Ivashka and Lukas Rosol respectively.
Richard Gasquet consigned Stan Wawrinka to an early exit at the European Open, coming from a set down to win 2-6 7-6 (7-4) 6-4 in a battle of two of the most experienced players on the circuit.
Fifth seed Dan Evans beat Tallon Griekspoor 6-3 6-4 in the first round in Antwerp, while his fellow Brit Jack Draper was an emphatic 6-1 6-2 winner against Jenson Brooksby of the United States.
World number four Medvedev fell to a 6-4 6-7 (7-9) 6-3 loss against three-time major winner Wawrinka, who will next meet Mikael Ymer after his straight-sets win over home favourite Gregoire Barrere.
Second seed Hurkacz did not experience such struggles against Thiem as the Pole cruised to a 6-3 6-4 as he served 12 aces in a dominant performance in Metz.
Hurkacz will face Arthur Rinderknech in the next round after the Frenchman battled to a 7-6 (13-11) 6-3 triumph over fifth seed Nikoloz Basilashvili.
Alexander Bublik, the seventh favourite in France, was also made to work for his progress to the quarter-finals, downing Emil Ruusuvuori 6-7 (4-7) 6-4 6-3.
Fourth seed Holger Rune awaits Bublik after Benjamin Bonzi retired due to injury when 6-4 4-1 down against the Dane.
Lorenzo Sonego coasted through his second-round clash to defeat Gilles Simon 7-6 (7-2) 6-4 to tee up a last-eight clash with Sebastian Korda.
Murray needed less than an hour to record a 6-2 6-0 triumph over the big-serving American, setting up a last-16 meeting with Australia's Max Purcell.
Three-time grand slam champion Murray hobbled out of his last meeting with Querrey at the Wimbledon quarter-finals in 2017, a defeat which marked the start of his injury woes.
But he produced a polished display on the grass to wrap up his eighth career win over the American on Tuesday.
Elsewhere in Rhode Island, eighth seed James Duckworth battled to a 6-2 4-6 6-2 win over Liam Broady, and seventh seed Jiri Vesely raced to a 6-4 6-2 triumph against Spain's Feliciano Lopez.
Meanwhile, Thiem ended a 426-day wait for a Tour-level win by overcoming Finland's Emil Ruusuvuori 3-6 6-1 7-6 (7-5) at the Swedish Open.
The Austrian, who has won 17 career titles, halted a run of 10 consecutive losses on the ATP Tour with his first triumph since he beat Marton Fucsovics at the last-32 stage of the Internazionali d'Italia in May 2021.
The 28-year-old expressed his delight at ending his drought in the aftermath, saying: "It's a long time. My last victory was in Rome in 2021, it feels like a different world somehow.
"Many, many things happened. It was tough, but it was also a very good experience I think, for life in general. I'm so happy that I got this first victory here today."
Thiem will face fourth seed Roberto Bautista Agut in the last 16, while Sebastien Baez will take on Alejandro Davidovich Fokina after the former beat Fabio Fognini in straight sets.
The round of 32 did see two shock exits, however, with seventh seed Holger Rune succumbing to a 6-3 6-3 defeat against Switzerland's Marc-Andrea Huesler, and Nikoloz Basilashvili being forced to retire at one set down against Hugo Gaston.
Also, Francisco Cerundolo beat Pedro Sousa to set up an enticing clash with top seed Casper Ruud.
Nadal will return after close to a year on the sidelines at the Brisbane International, which runs from December 31 to January 7, as he targets a bid for a 23rd grand slam title at Melbourne Park later in January.
The 37-year-old has not competed since this year's edition of the Australian Open, having suffered a hip injury during a surprise second-round defeat to Mackenzie McDonald.
Nadal attempted to recover from his injury before the start of the French Open in May, only to be forced to withdraw from that tournament and undergo season-ending surgery.
The 'King of Clay' has said 2024 will likely be his final year on the tour, and while Rune accepts it will be difficult for Nadal to recapture his best form, the Dane is excited to see how he fares.
"It's great for tennis that Rafa is coming back," Rune said. "It brings even more fans to the tournaments and more excitement for the sport. I think this is good.
"We're going to have Novak [Djokovic], Rafa, [Carlos] Alcaraz, [Jannik] Sinner and more guys for the Australian Open. That's going to be super fun and it's exciting to see how it's going to go.
"You see some videos where he's practicing hard, but of course it's always difficult to come back and play after so long. But I'm excited to see it."
Jack Draper was the last player to lose to Nadal, going down in four sets in the first round of the 2023 Australian Open, and he is keen for a chance to avenge that defeat next year.
"I mean, I think it's amazing for tennis. Obviously, he's put in a lot of hard work to be back on tour, I'm seeing lots of videos of him training very intensely," Draper said.
"It's just good for the spectators, the players, that someone of his calibre – one of the greatest of all time – is back playing.
"I hope I get a chance to play him again because I think I was one of the last people to play him. It'll be amazing to have him back on the tour."
World number 32 Alexander Bublik echoed those sentiments, adding he was excited to see who will have the honour of being Nadal's final opponent if – as expected – he retires next year.
"Of course, it's very exciting that Rafa is coming back," Bublik said. "He's a legend of our game.
"But I just discussed it with Holger… I'm more excited to think who is going to play him in his last match, who he's going to finish such a legendary career against.
"So for me, it's an exciting time. We'll see how he comes back but he's going to bring a lot to the game."
The 20-year-old Dane came through 6-2 4-6 6-2 against the defending champion in a rain-hit encounter in Rome.
Seventh seed Rune raced through the opening set in 39 minutes before Djokovic was seen to by the physio early in the second and given some medication before the weather forced play to be suspended.
Top seed Djokovic – who beat Britain’s Cameron Norrie in a feisty fourth-round match – levelled the match soon after the resumption, but it was Rune who pulled clear in the decider.
Rune, making his tournament debut, opened a 4-0 lead after a double break before closing out the match for successive victories in his matches against the Serbian.
“It’s really a big win for me,” Rune said in his on-court interview.
“Obviously I did it last year in Paris as well, but every match is a huge challenge for me when I play against Novak.
“He is one of the greatest that’s ever played the game. I knew I had to be at my best and I said it yesterday, and I was today.
“I am super proud of myself and I enjoyed every moment out there, but I stay humble of course. I have a lot to achieve.”
Djokovic is chasing a record seventh title but again found 20-year-old Rune, who is making his debut at the eight-man event, a troublesome opponent before pulling off a third win in five meetings.
It was past midnight in Turin when Djokovic completed a 7-6 (4) 6-7 (1) 6-3 victory after three hours and four minutes on court.
Rune has fared much better against Djokovic than most of his rivals over the last couple of years, beating him in Paris last autumn and Rome in the spring before a narrow defeat in the French capital a week-and-a-half ago.
The Serbian went on to claim the Masters series title, maintaining his record of not having lost a match since the Wimbledon final.
It was Rune who struck first with a break to lead 3-2 but Djokovic hit straight back and the high-class set went all the way to a tie-break, which the top seed took with a forehand smashed cross-court past his helpless opponent.
Rune reacted well, breaking again to lead 2-0 in the second set, but once more Djokovic found the immediate response, and a strong serve foiled the young Dane when he forced a set point at 4-5.
Rune slumped after reaching the Wimbledon quarter-finals prior to hiring Djokovic’s former coach Boris Becker last month, but there were plenty of moments here to demonstrate his huge talent and fearsome ball-striking.
He has won at least a set against Djokovic in every match they have played, but he had a helping hand in setting up a decider, his rival playing a highly unusual lacklustre tie-break.
Djokovic broke straight away to start the deciding set, only for this time Rune to recover the deficit immediately, prompting a frustrated Djokovic to stamp on two rackets, snapping the frames.
But he broke again to lead 4-2 and this time there was no way back for Rune.
Djokovic told Prime Video: “It took everything. I saw in the first game when he fired shots from the baseline, I knew it was going to be a tough night for me. I thought he played great. I played great in some moments.
“Overall a win is a win. It was a very emotional win and a tough win knowing the significance of tonight’s match. After a really terrible second-set tie-break I think I played a really solid third set.”
Earlier, Italian Jannik Sinner delighted the crowd by defeating Stefanos Tsitsipas in the opening singles match.
Sinner, 22, played as an alternate two years ago but qualified for the first time this season after claiming four ATP Tour titles and rising to world number four. He is one of the favourites to lift the trophy this week, which would be the dream scenario for the home fans, and a 6-4 6-4 victory over Tsitsipas is a big step towards the semi-finals.
Paul edged the third seed 6-3 6-7 (2-7) 7-6 (7-2) in three hours and 29 minutes in their semi-final clash in Acapulco.
World number 23 Paul actually generated a match point late in the second set but spurned his initial chance, then waiting another two hours before winning in the third-set tie-break.
Paul let match point slip at 5-4 in the second set and had to rally back from 3-1 down in the third, but triumphed on his fourth match point.
"I couldn't be happier," Paul said. "The goal for this year was to get the ranking up and get more trophies. I only have one trophy on Tour between singles and doubles.
"You don't get trophies unless your in the final, and hopefully I can play another good match tomorrow and get the winner's trophy."
The 2023 Australian Open semi-finalist will take on Alex de Minaur in Saturday's decider, after he defeated Holger Rune 3-6 7-5 6-2 in two hours and 50 minutes.
In the Chile Open, local Nicolas Jarry progressed into the semi-finals with a 3-6 6-3 6-4 win over German qualifier Yannick Hanfmann. Jarry will face Spaniard Jaume Munar after he won 6-3 3-6 6-2 over Thiago Monteiro.
Third seed Sebastian Baez got past Laslo Djere 7-6 (7-4) 6-4, setting up a semi-final date with Tomas Martin Etcheverry after he won 6-1 6-2 over Dusan Lajovic.
The 25-year-old Russian has 12 tournament wins to his name, but all have come at ATP 500 or ATP 250 level, respectable but lower rungs than this tier.
Rublev lost to Stefanos Tsitsipas in Monte Carlo in 2021 and to Alexander Zverev in Cincinnati in the same year, as he failed to capitalise on two chances to break his Masters 1000 duck.
Now comes another opportunity on the clay against teenager Rune on Sunday, after both men ground out tough semi-final comeback wins.
Rublev beat Taylor Fritz 5-7 6-1 6-3, while Rune fought back gallantly to overcome Jannik Sinner 1-6 7-5 7-5, with rain delays affected both matches on Saturday.
Rublev is full of appreciation for Rune's game. They met at the last-16 stage of the Australian Open in January, with Rublev winning a marathon clash in a dizzying final-set tie-break.
Their only other previous clash came indoors at the Paris Masters last November, with Rune taking that third-round match in straight sets and going on to win the title as an unseeded player, beating Novak Djokovic in the final.
Rublev said of Rune: "Holger is the guy who runs a lot, and he runs really well. He read the game really well. He's very talented.
"He has a good touch. He doesn't give you any rhythm, because as soon as he has a chance he tries to do drop shots, he tries to hit full power, goes to the net, returns and goes to the net, then serves to the net.
"He doesn't give you rhythm to put pressure on him to play your style."
Rune sees Rublev as a major threat to his prospects of a second title at this level, but the 19-year-old Dane is not short of self-belief.
"I expect for myself to push full. It's the last push, it's the last match of the tournament," Rune said. "Obviously he had three sets as well, so he must be feeling the legs a little bit, I hope.
"It's going to be great. We've played each other twice. It's one-all head to head, so it's going to be interesting, for sure.
"I've just got to stay in the moment, go for it against the best players in the world, and Andrey has been showing that for many years now, he's been top five, six for many years, so I've got to play my best. I've got to take it, because he's not going to give it to me."
Second seed Rublev won this event two years ago but there will be no such run this time around after his 6-4 6-4 loss on Wednesday.
De Minaur broke the world number five early in each set and sealed the win at the first time of asking, moving to a 3-0 head-to-head record against Rublev on hard courts.
The Australian will face Maxime Cressy in the next round, who bounced back from his Open Sud de France final defeat by beating Tim van Rijthoven.
Jannik Sinner saw off Cressy in that Montpellier showdown and the Italian carried that form into this tournament, though he needed three sets to overcome Benjamin Bonzi.
Frenchman Bonzi forced a decider but Sinner regained his composure in the final set to prevail 6-2 3-6 6-1 and set up a heavyweight clash with top seed Stefanos Tsitsipas.
There was no such progress for Alexander Zverev, who joined Rublev in suffering an early exit.
The German came unstuck 4-6 6-3 6-4 to home favourite Tallon Griekspoor, whose four wins over top-20 opponents have all come in Rotterdam.
Stan Wawrinka, the champion in 2015 and runner-up four years later, will face the winner of that tie, after he beat Richard Gasquet 6-3 6-3 to reach the quarter-finals.
Holger Rune reached the semi-finals in Montpellier, and like Sinner the fourth seed progressed into round two, claiming a routine straight-sets victory over qualifier Constant Lestienne.
"It was tricky. It's a lot about finding the rhythm here in the beginning of the tournament and first match you have to really be on your toes, especially I played a qualifier today who already has two matches in his bag," Rune said.
"It made it more difficult, but I'm happy how I handled every situation today."
Hubert Hurkacz was another seed to fall out, with the world number 10 going down 7-6 (7-4) 7-6 (7-5) to Grigor Dimitrov.
Having done the same in his semi-final against Taylor Fritz, Rublev showed grit and determination to do so again in the final, eventually winning 5-7 6-2 7-5.
Rublev become only the third player in the Open Era to have comeback wins in both the semi-final and final at Monte Carlo after Ivan Lendl (1988) and Ilie Nastase (1971).
Rune started the stronger of the two and forced a break in the sixth game of the first set with two delightful drop-shot winners, only for Rublev to break straight back in the next game.
After throwing away seven of eight break point chances in the first set, it was somewhat inevitable Rublev was unable to save a crucial one on his own serve with Rune at set point, sending a return long to hand the Dane the first frame.
This was Rune's sixth ATP Tour-level final, making him the fifth teenager to pass five since 2000.
Rublev seemed determined not to make the same mistake again as he immediately broke Rune's serve in the opening game of the second set, although he did pass up two chances for a double break before Rune levelled the set at 2-2.
The heat appeared to be affecting both players' service games in a high-octane encounter, but Rublev steadied himself before breaking again and then racing to another as he comfortably secured the second set.
As Rublev had done after dropping the opener, however, Rune responded defiantly and raced out to a 3-0 lead in the decider, but after missing a chance to go 5-1 up, he was broken back as Rublev came back to 4-4.
At 5-5, a tiring Rune twice hit the net with overhead smashes and then had a double fault at break point, leading to a crucial break for the Russian, who then served out the match to clinch the title.
"I know it's tough to lose a final, but you are too freaking young, man, and already have a Masters 1000 title, so give me one time to win it," Rublev joked with a smiling Rune at the trophy presentation.
The top seed in 2023, Rune won his first career title at this event last year, albeit only after Van de Zandschulp retired from the final with chest pains.
It was "probably the worst way to win a final", Rune said back then, so Sunday's 6-3 1-6 7-6 (7-3) victory would have felt especially sweet.
Van de Zandschulp's only career final appearances have been in Munich, meaning he is still waiting for a first title. That wait should have ended here.
Rune took the opening set, breaking immediately, but the fourth seed roared back in the second to tee up a decider.
Momentum was with Van de Zandschulp, who broke twice and forged a pair of match points.
Both were squandered, however, and Rune recovered to tie the set, then did so again when Van de Zandschulp broke into the lead once more and created two more match points.
That meant a tie-break, in which Rune swiftly gained control and held off the giant Dutchman for a hard-earned win.
