Los Blancos won the competition three seasons running prior to being dumped out at this stage by Ajax last year, while City have never previously gone all the way.
Here, Sports Mole selects a combined XI, using only the players who are expected to be available for the midweek clash.
Thibaut Courtois has kept two more clean sheets than Ederson this season and Madrid boast one of the meanest defences on the continent, even if they have gone off the boil of late.
City left-back Benjamin Mendy has had another injury-plagued campaign and Kyle Walker is no longer the force he once was. The same could be said of Marcelo in many ways, but he gets the nod here, as does defensive teammate Dani Carvajal.
When fully fit there are not many better centre-backs on the planet than Aymeric Laporte, yet two of them just happen to play for Madrid. Raphael Varane is a regular for France, whereas Laporte cannot squeeze his way into Didier Deschamps' thoughts, while Sergio Ramos has a knack of frustrating attackers and scoring key goals.
We are going with a 4-2-3-1 formation, which allows pass master Rodrigo to partner a midfield destroyer in Casemiro. Both players have their own skillset and, used together in the engine room, will allow those further forward to work their magic.
Kevin De Bruyne was arguably the first name on the teamsheet given his form this campaign, with the Belgian boasting eight goals and 16 assists in the Premier League alone. Raheem Sterling is returning from injury and, while he has not been at his best over the last couple of months, he is still an incredible talent that provides more than the likes of Vinicius Junior, Isco and Rodrygo Goes.
It would be easy to select Riyad Mahrez on the other flank, or indeed a player of Gareth Bale's ability, but to provide the team with some balance we are opting for Federico Valverde, who has more than held his own in some big matches this term.
That leaves one spot up for grabs in attack and it is a straight shootout between Karim Benzema and Sergio Aguero. On paper there is very little to choose between the two as they boast 17 and 18 goals in their respective leagues and Champions League combined this term. Aguero has failed to score in his last four matches, but Benzema is on an even worse run so the Argentina international is our choice.