Here, the PA news agency looks at some talking points ahead of the game.
City's best chance yet
It is not something the top brass at City openly – or at least regularly – admit, but the Champions League is widely believed to be the club's Holy Grail. With four Premier League titles in the modern era, transferring their domestic dominance onto the European stage is the next logical step in both their on-field and off-field development. There is a strong argument to say the new last-eight format, with all ties over one leg, in one city, in a short space of time, represents their best opportunity yet. Two-legged ties have been their undoing in recent years while one-off cup ties have been something of a speciality.
Eyes on Guardiola
It is generally acknowledged that City brought in Pep Guardiola with this competition in mind. The Catalan is undoubtedly one of the greatest managers of his era but it is now nine years since the second of his two triumphs with Barcelona and, with his future beyond next season uncertain, time could be running out. All eyes will be on him to see if he can crack it this time after previous failures at the last-16 stage (Monaco in 2017) and quarter-finals (Liverpool and Tottenham in 2018 and 2019 respectively) with City. In the past he has been accused of "over-thinking" matters – something that may not be an issue in the streamlined one-leg format.
City's record goalscorer Sergio Aguero has been in a race against time to be fit for the latter stages of the competition after undergoing knee surgery in June. He has not yet been ruled out of the semi-finals, should City progress, but it is looking increasingly unlikely he will play any part in the tournament. With the player still in Barcelona receiving treatment, the Lyon clash clearly comes too soon.
Can De Bruyne do it again?
Kevin De Bruyne has been City's outstanding player this term and the challenge for him now, to elevate himself to the status enjoyed by the game's elite, is to deliver on the biggest Champions League stage. The Belgian playmaker was involved when City reached the semi-finals under Manuel Pellegrini in 2016 but that is the only time he has gone deep into the competition.
Central defence has been City's weak spot all season – a fact recognised by the recent signing of Nathan Ake while the club continue to be linked with Napoli's Kalidou Koulibaly. With Ake not eligible until next season, Guardiola reverted to playing experienced midfielder Fernandinho alongside Aymeric Laporte against Real Madrid last week. That appears to be the most likely line-up again with youngster Eric Garcia's recent breakthrough undermined by his refusal to sign a new contract amid links to Barcelona, and with John Stones and Nicolas Otamendi not wholly trusted.