England and Italy were drawn alongside Ukraine, North Macedonia and Malta in a challenging qualification group on Sunday, from which the top two will qualify automatically for the tournament in Germany.
The duo met as recently as last month, when Giacomo Raspadori's goal condemned England to relegation from the top tier of the Nations League, while Mancini also led the Azzurri to victory over the Three Lions in last year's Euro 2020 final.
England's dismal Nations League campaign meant they – alongside world champions France – were in pot two for the draw in Frankfurt.
Although Mancini claims he expected Italy to land one of those two giants, he remains content with the draw and is looking forward to meeting Gareth Southgate's men.
"I was sure we would have one between England and France, but that's okay too," Mancini told Rai Sport after the draw.
"It's a group of five, it's doable. But there won't be simple games, they'll all have to be played.
"It will certainly be beautiful with England, with Southgate we know each other and if it continues like this we are pretty good, I don't know if he agrees.
"By now this challenge is a classic and, although we faced each other 20 days ago, it will be nice to meet again."
While Italy have happy memories of their recent games against England, remaining unbeaten in their last six head-to-head meetings, the same cannot be said about another of their opponents.
North Macedonia clinched a stunning win over Italy in the World Cup play-offs in March, ensuring the Azzurri missed out on a second consecutive edition of the tournament.
Mancini is urging caution ahead of that reunion, adding: "It's one of those games that happen every now and then. As we saw in Palermo, all matches must be played, even the simplest ones."
The Azzurri boss was also pleased to be drawn alongside Ukraine, declaring: "There will be some emotion... but Ukraine is still a good national team."
Eljif Elmas scored late on in Duisburg - Ilkay Gundogan having earlier cancelled out Goran Pandev's opener from the penalty spot - to inflict a first World Cup qualifying defeat on Germany since September 2001 - a run spanning 35 matches.
The defeat leaves Die Mannschaft third in Group J, level on points with North Macedonia and three points behind pacesetters Armenia, who have won all three matches so far.
Speaking to RTL after the game, Bayern Munich honorary president Uli Hoeness suggested Low - who has announced he will end his tenure as head coach after Euro 2020 - should bring Muller and Hummels back into the national team.
The duo, as well as Bayern defender Jerome Boateng, have not played for their country since November 2018, but Low recently hinted each player remains in his plans for this year's tournament.
"Hummels is a player with strong aerial ability and someone who has a lot of experience," Hoeness said. "He can definitely give this team something.
"Muller also definitely belongs in the squad. He's always good for goals and can help any team in the world in certain situations."
But when asked again about those absent players after the North Macedonia game, Low told RTL: "This question cannot be answered now. The decision will be made in May. It is something to think about in the next few days and weeks."
The defeat for Germany was just their third ever in World Cup qualifying and leaves them with work to do when they resume their campaign in September.
There may well have been a different outcome on Wednesday had Timo Werner made more of a glorious chance that fell his way five minutes before Elmas' winner, the substitute forward dragging wide in a one-on-on opportunity.
"He has to score that, no question about it," Low said of Werner's late miss, coming from the Chelsea attacker's only touch of the ball in the opposition penalty area.
"He doesn't hit the ball properly, otherwise it's a goal. Timo blames himself the most. That was a bad moment in a period in which we were on top in the game."
Low had previously criticised his players for their profligacy in the 1-0 win over Romania on Sunday, which followed on from a 3-0 victory at home to Iceland.
Germany had 11 shots against North Macedonia but tested visiting goalkeeper Stole Dimitrievski with just two of those, with Serge Gnabry - the match-winner against Romania last time out - wasting two chances of his own in the first half.
"There is no magic formula," Low said. "You can train all you want, but it is difference in a competitive match. We were too hesitant to finish.
"We weren't consistent. With the score at 1-1, Timo had that huge chance. We have to look back at the chances and talk about it."
Gundogan had drawn Germany on level terms but his side were caught out at the back for a second time for the winning goal.
"The fact is, that should not be happening," Gundogan said. "It felt like they were in front of our goal twice and scored twice - it was too easy for them.
"We had many chances and only scored one goal. We didn't defend well with either goal - twice they had a man in the middle completely free.
"I leave with a bad feeling. It hurts all the more that we won't play again for three months. We have to get in top form by the end of May and prepare for the Euros."
The teams faced each other in the Euro 2020 final at Wembley Stadium last year, with Italy emerging victorious on penalties to win their first European Championship trophy since 1968 and deny England their first major title in 55 years.
The sides also met twice in the recent Nations League campaign, playing out a goalless draw at Molineux in June before Giacomo Raspadori gave Italy a 1-0 triumph in the return fixture at San Siro in September.
The Three Lions have not beaten Italy in six attempts since a 2-1 victory in 2012, and Southgate says that run needs to end.
"England's record against Italy generally is not very good," Southgate told Sky Sports. "So we've got to improve that.
"There's not too many surprises, they've changed the team a lot for all of those different matches.
"We know the quality they have, we know the depth that they have."
England and Italy have been drawn in Group C alongside Ukraine, Malta and North Macedonia, the latter of whom knocked the Azzurri out of the World Cup play-offs earlier this year, preventing the European champions from making it to Qatar.
Southgate acknowledged the overall difficulty of the group, adding: "It's clearly a tough draw, given the quality of the opposition.
"But we've had draws in qualification that have probably been a little bit more comfortable than that, although I'd have to say Poland and Hungary in the last qualifying group was particularly tough as well, so we're used to that.
"The draws are what they are, it's how you perform on the day."
