Spurs have a 1-0 lead following the first leg.
Here, Press Association Sport looks at some talking points ahead of the game.
Can City turn it around?
To keep their quadruple hopes alive City will need to change their approach from the conservative system they adopted in the first leg. Then Pep Guardiola left out Kevin De Bruyne and deployed two holding midfielders in what seemed a damage limitation exercise. Something more like the normal attack-minded formation that serves so well in the Premier League will be expected, and probably required, to ensure City get on the front foot this time.
Mauricio Pochettino‘s men hold the upper hand after successfully cancelling out City last week. Playing a high-energy, high-pressing game, Spurs gave City some of their own medicine. Whether they can repeat the trick against a City side set out to attack more is debatable, however. Spurs may be forced to play a more containing game. They will want their midfielders to come to the fore and try to dictate affairs.
Spurs are without their talisman Harry Kane, who was forced off with an ankle injury in the first leg. They need someone to fill that void. When Kane was out earlier in the season, Son Heung-min stepped up and it was also the Korean who grabbed the winner last week. Lucas Moura then shone at the weekend, netting a hat-trick against Huddersfield, and he will hope for another chance.
Watching City and Spurs, two of the most attractive sides in the Premier League, attack each other at full throttle is the type of fare that makes that competition so appealing. Yet both sides will need to be aware this is not a Premier League game and it will be refereed differently. Most notably this season – as Danny Rose discovered in the first leg and Nicolas Otamendi did in the last round at Schalke – UEFA are operating a much stricter interpretation of handball. With VAR in operation, there is almost no escaping punishment if the ball strikes the arm in the area. On top of this, the Turkish officials in charge will view certain matters in a different light to how their English counterparts would.
Impact on Saturday’s game
The game is actually only the second instalment of a three-parter. The trilogy concludes with Spurs returning to the Etihad in the Premier League on Saturday. That game will also have plenty riding on it, with City involved in a tight title race with Liverpool and Spurs under pressure to hold onto their top-four place. The psychology could be interesting, with the victor on Wednesday having gained an edge but the loser having incentive to seek revenge, while there could also be a further physical toll.
How Man City could line up against Tottenham