The perennial French champions welcome United to the Parc des Princes looking to extend a run of five successive wins across all competitions and gain a measure of revenge over their visitors.
The last time the two sides met, in March 2019, United pulled off a 3-1 victory in the French capital to progress to the quarter-finals on away goals against all the odds.
Here, Sports Mole looks at how Thomas Tuchel could set his side up for Tuesday night's mouthwatering showdown.
Tuchel is facing something of an injury crisis ahead of this match, even claiming last week that he may only have 11 fit players for the visit of United.
Mbappe scored twice in his absence on Friday to make it four goals and three assists in his four Ligue 1 outings this term, and should he score again on Tuesday night then he would become the youngest ever player to score 20 Champions League goals, breaking Lionel Messi's record.
Completing the star-studded front three is former United winger Angel Di Maria, who provided more assists than anyone else in the Champions League last season and is available after sitting out the Nimes game through suspension.
Layvin Kurzawa is also back after a domestic ban, although defensively there are a number of injury concerns.
Marco Verratti has been ruled out and Marquinhos remains a doubt, which could open the door for former Everton midfielder Idrissa Gueye to start in midfield alongside another Man United alumnus in Ander Herrera.
Julian Draxler also has a question mark hanging over his head, while Danilo Pereira missed out on Friday having been in contact with a coronavirus-infected Cristiano Ronaldo on international duty, although he should be available for this match.
Juan Bernat is a long-term absentee, while Thilo Kehrer, Mauro Icardi and Leandro Paredes have also been ruled out of this contest.