Pep Guardiola's side will head into the match full of confidence after the comfortable weekend victory over Manchester United but know they will likely face a tougher test against the current Serie A champions.
There will be plenty of interest as Kevin de Bruyne returns to Manchester just months after he was released by City, while former United midfielder Scott McTominay and forward Rasmus Hojlund will hope to steal the headlines as well.
From a City perspective, Erling Haaland and Phil Foden will both hope to keep their fine form going, though Rodri will need to show signs of improvement after a sloppy display last weekend.
Here is how we think City should line up against Napoli:
Donnarumma is the No.1 and should keep his place in goal against Napoli.
1. GK - Gianluigi Donnarumma
Donnarumma is the No.1 and should keep his place in goal against Napoli. | Getty Images
Lewis could start against Napoli to rest Khusanov for the Arsenal match.
2. RB - Rico Lewis
Lewis could start against Napoli to rest Khusanov for the Arsenal match. | Getty Images
Dias is the obvious choice in central defence and there is no reason to rest him.
3. CB - Ruben Dias
Dias is the obvious choice in central defence and there is no reason to rest him. | Getty Images
Gvardiol is best as a central defender and should play there again in midweek.
4. CB - Josko Gvardiol
Gvardiol is best as a central defender and should play there again in midweek. | Getty Images