City recorded an impressive victory when the pair met at the Bernabeu back in February, meaning that Madrid have plenty to do if they are to advance to the quarter-finals of the competition once again.
It would be fair to say that it has not quite been the season that the City supporters would have been hoping for. Indeed, in addition to giving up the Premier League trophy to Liverpool, the Citizens suffered a 2-0 defeat to Arsenal in the semi-finals of the FA Cup as they surprisingly bowed out.
Pep Guardiola's side did lift the EFL Cup courtesy of a 2-1 win over Aston Villa back in March, but it would go down as a disappointing campaign if that was the only silverware that they were to secure in 2019-20.
The English giants are in a strong position to reach the quarter-finals of the Champions League, though, holding a 2-1 advantage from the first leg of their last-16 clash with Madrid at the Bernabeu. Isco sent Los Blancos ahead on the night, but City answered back through Gabriel Jesus and Kevin De Bruyne.
City would have been feeling good about themselves after the first leg, but there is a degree of uncertainty heading into the reserve match due to what has transpired across the world of football in recent months.
City ended their Premier League season with a thumping 5-0 win over Norwich City, which saw them finish on 81 points, 18 behind champions Liverpool in the Premier League table. They have been full of goals since returning to the field in June but have also lost to Chelsea, Southampton and Arsenal.
The Citizens were beaten by Tottenham Hotspur in the quarter-finals of last season's competition, while they have only won one of their five two-legged knockout ties against Spanish opposition, losing each of their last four, which will be a concern as they prepare to welcome the reigning La Liga champions.
City's last home game against a Spanish club saw them lose 3-1 to Barcelona in the group stages of the 2016-17 competition, although they have won four and lost just two of their nine previous home matches against teams from Spain.
Guardiola's side will be the favourites to progress considering what happened in the first leg back in February, with the onus very much on Madrid to turn the tie around. The special circumstances surrounding the contest means that anything is possible, though, and it remains to be seen whether the Manchester giants can hold off the threat of Los Blancos to advance to the final eight once again.
Madrid's stunning form post-lockdown saw them wrestle the La Liga title away from Barcelona, ultimately finishing five points clear at the top of the table. Los Blancos actually won 10 straight games in the league before ending their domestic campaign with a 2-2 draw at Leganes on July 19.
Zinedine Zidane's side have had longer than City to prepare for this match; in fact, the English side have played twice in the Premier League since Madrid last took to the field, although it remains to be seen whether that helps or hinders either club on Friday night.
The visitors will be without the inspirational Sergio Ramos for this game, but it has been a real team effort from the capital giants since returning to the field in June, and there is no question that they will fancy their chances of causing problems to a City defence that continues to show deficiencies.
Last season was actually the first time since 2009-10 that Madrid failed to reach at least the semi-finals of the competition as they bowed out to Ajax in the round of 16, and an exit at this stage would have to go down as another huge disappointment considering their pedigree in the competition.
Zidane's team picked up 11 points in the group stages of this season's competition to finish second behind Paris Saint-Germain in Group B, meaning that they have been runners-up in their group in three of their last four campaigns, which is somewhat of a surprise considering their success.
Madrid have won their last seven away matches in the round of 16, though, while they have been victorious in 16 of their last 25 European away fixtures, suffering just five defeats, which is a brilliant record at this level.
The Spanish outfit have also won eight of their 12 two-legged knockout ties against English clubs in European competition, notably overcoming City in the semi-finals back in 2016 courtesy of a 1-0 success.
That said, only on one previous occasion have Madrid lost the home first leg of a European tie and still managed to progress, which occurred back in 1971. A 1-1 draw in the reverse match at the Bernabeu would not have been the end of the world for Los Blancos, but De Bruyne's penalty seven minutes from time means that City have room for error in the second leg in Manchester.
Man City Champions League form: WWDDWW
Man City form (all competitions): WWWLWW
Real Madrid Champions League form: DWWDWL
Real Madrid form (all competitions): WWWWWD
Joao Cancelo started at left-back against Norwich City last time out and that could again be the case here, while Gabriel Jesus is likely to continue at the tip of the attack.
Rodri and Ilkay Gundogan should join De Bruyne as part of a midfield three, while Riyad Mahrez could get the nod over the likes of Phil Foden and Bernardo Silva to start alongside Jesus and Raheem Sterling in attack.
As for Madrid, inspirational captain Ramos will miss out through suspension due to the red card that the Spaniard picked up the first leg at the Bernabeu. As a result, Eder Militao could join Raphael Varane in central defence, while Ferland Mendy should get the nod over Marcelo at left-back.
Federico Valverde could start on the bench as Toni Kroos and Luka Modric have both been in impressive form since the lockdown period, while Zidane has decisions to make in the final third of the field.
Hazard has only scored once for Los Blancos this term and was not involved in his side's last league game of the season against Leganes on July 19. The former Chelsea attacker has been in full training ahead of this contest, though, and is likely to be handed a spot on the left.
Man City possible starting lineup:
Ederson; Walker, Fernandinho, Laporte, Cancelo; Rodri, Gundogan, De Bruyne; Sterling, Gabriel Jesus, Mahrez
Real Madrid possible starting lineup:
Courtois; Carvajal, Varane, Militao, Mendy; Casemiro, Modric, Kroos; Hazard, Benzema, Asensio
Head To Head
These two sides have met on five previous occasions, with Madrid leading the head-to-head record two victories to one, while there have also been two draws.
The pair first locked horns during the group stage of the 2012-13 competition, with Madrid running out 3-2 winners at home before a 1-1 draw in the reverse game at the Etihad Stadium.
The last meeting between the two sides came in the semi-finals of the 2015-16 competition, and the Spanish giants advanced to the final courtesy of a 1-0 aggregate success.
City's 2-1 victory in the first leg in February was therefore their first success against the capital giants.
We say: Manchester City 2-2 Real Madrid (City 4-3 on aggregate)
There is no question that Madrid are capable of turning this tie around, but we are finding it difficult to back City to lose at the Etihad Stadium, even taking into account their problems. It would not be a surprise to see this game run into extra time and possibly penalties, but we are backing a 2-2 draw on the night, which would see Guardiola's side advance into the quarter-finals of the competition.