Pep Guardiola is still searching for his first European crown since taking the reins at City, with the Premier League giants being sent packing by Lyon at last season's quarter-final stage, and the illustrious Spaniard is yet to guide City past the last eight following his arrival in 2016.
City have also faltered in the early stages of the new Premier League season - losing to Leicester City at home and being held to a draw by newly-promoted Leeds United - but Guardiola's men go into Wednesday's showdown following a 1-0 win over Arsenal courtesy of a Raheem Sterling strike.
Here, Sports Mole looks at how City could line up for their inaugural Champions League clash of the season.
Guardiola opted to line up in a 3-1-4-2 formation against the Gunners, a system which ultimately worked to great effect as the Citizens walked away from that encounter with all three points despite having to contend with a number of missing players.
However, that same formation is the one that the City manager came under heavy scrutiny for in their quarter-final defeat to Lyon in the 2019-20 campaign, and Guardiola may decide to revert back to a tried-and-tested four-man defence here.
With regards to absentees, Kevin De Bruyne, Gabriel Jesus, Aymeric Laporte, Benjamin Mendy will all be forced to sit out the visit of Porto, and it would not be a surprise to see Guardiola shuffle the pack as he has so often done during his time in the Etihad dugout.
That could see the inclusions of Ferran Torres and Ilkay Gundogan from the first whistle, with the latter coming off the bench for the final 25 minutes against Arsenal after recovering from coronavirus, whilst Torres is in contention to replace Riyad Mahrez on the right flank.
Sergio Aguero came under fire after touching lineswoman Sian Massey-Ellis during City's win over the Gunners - the Argentine's first outing since June after returning from a knee problem - but Aguero will face no retrospective action following that incident and is set to lead the line here in place of the injured Jesus.
Nathan Ake and Joao Cancelo demonstrated their versatile qualities at the weekend but may return to more familiar defensive positions here, although Guardiola has confirmed that Oleksandr Zinchenko is back fit and ready to be called upon for the visit of Porto.