Pep Guardiola's side will also enter the match off the back of a thumping 5-0 win over Burnley in the Premier League at the weekend and will therefore be full of confidence as they look to overcome Shakhtar in Ukraine.
That said, it will prove to be a tough assignment against a team who sit top of their domestic league, and have plenty of European experience.
Here, Sports Mole looks at how City could line up in Ukraine.
Kevin De Bruyne made his comeback from a knee injury against Burnley at the weekend, and the Belgium will be under consideration to start this match.
Kyle Walker and Benjamin Mendy should continue in the full-back positions, but De Bruyne's introduction could see Bernardo Silva drop out, despite the Portugal international impressing once again in City's five-goal showing on Saturday.
Leroy Sane is currently negotiating a new contract with City as the German shows signs of rediscovering his form from last season, and the 22-year-old should start on the left of a front three.