Vinicius Junior saw his stunning opening goal canceled out by a sweet Kevin De Bruyne effort to level matters.
Madrid are seeking a record-extending 15th Champions League title, while City have never won a title in their history.
However, Man City are full of confidence after they have managed to put together a 22-match unbeaten run heading into this game.
Even more impressive, Pep Guardiola’s side have won all of their last 15 games played at the Etihad.
But Madrid have won their last two away games in knock-out matches against English opponents in the UEFA Champions League, securing victories against Chelsea and Liverpool this season.
A repeat of last season’s 4-3 Etihad extravaganza would do for Man City lest they risk forming an unwanted trifecta with their Big Six rivals.
Guardiola has lost three of his last seven games against Los Blancos as a manager and will hope this can turn around to get a positive result.
City are unbeaten in their last 25 home games in the Champions League, with their previous such defeat coming at the hands of Lyon in 2018.
This is a difficult one to call but what do you think the result will be? Click here to place your bet on this game.
What time does Man City vs Real Madrid start?
The game kicks off at 21:00pm CET at the Etihad Stadium.
Man City vs Real Madrid team news
Midfield maestro Kevin De Bruyne was rested over the weekend and will return here, as well as Jack Grealish and Bernardo Silva.
Nathan Ake is being assessed but may sit this one out as Manuel Akanji and Kyle Walker both start.
Erling Haaland will continue to lead the attacking line as he seeks to further extend his exemplary goal-scoring run.
For the visitors, no change is expected from the starting XI that was took to the field in the first leg last week.
Man City vs Real Madrid head to head
These sides have gone up against each other 11 times with both winning 4 times, and the remaining three have resulted in a draw.
Man City vs Real Madrid current form
The hosts have won all but one game in their last five, which was the 1-1 draw against Real Madrid who have won 3 times and lost once in that run.
Man City vs Real Madrid prediction
Just like the first leg, both teams are tipped to score with over 2.5 goals expected in this game.