Roberto Mancini's City are unbeaten in 15 matches in European competition at Eastlands and host Group D rivals Borussia Dortmund knowing now is not the time to see that record ended.
The thrilling if ultimately heartbreaking result against Real Madrid means that City need to win against the Germans - a draw is probably not good enough as it would hand Dortmund a significant advantage in the group after their win over Ajax.
City should be buoyed by the knowledge that Dortmund have struggled away from home this season while the Etihad Stadium continues to be the bedrock of their campaigns.
For some such as former England, Aston Villa and Watford manager Graham Taylor, this season is also an important one for City to demonstrate that they can turn their riches into season-on-season success - and he argues that they have not done so yet.
Taylor, speaking at the launch of a new partnership between the Irish FA and Precision Training in Belfast, said: "My feeling about City is yes they won the Premier League but I don't see them yet as a real settled unit.
"They have good, capable players but I don't see them as a Manchester United-type of team capable of winning a trophy every season.
"They have some way to go before they can say they are the number one club in Manchester, never mind the country."
The clubs have never met before, but Dortmund have played in Manchester - including their first European away match at City's old Maine Road stadium against Manchester United in the 1956/57 season.
Dortmund have not enjoyed good fortune in England recently however - they were defeated 2-1 at Arsenal last season, when they lost all three away fixtures in the group stage, and have also lost their last three games in England.
City will certainly need to improve defensively - the best defence for the last two seasons has yet to keep a clean sheet in this campaign and Mancini has expressed concern at their vulnerability from set-pieces.
City keeper Joe Hart accepts that needs to change, saying: "We keep getting into positions where we can win and we need to win to do what we want to do, so we have to keep clean sheets - that includes me and the whole team."