The Premier League leaders have won 14 games in a row in all competitions, though they face a potentially tricky test against fellow in-form side Swansea.
City took a potentially decisive hold on the Premier League title race with a 4-1 win at reigning champions Liverpool on Sunday evening, helped by two horror moments from opposition goalkeeper Alisson Becker.
Ilkay Gundogan scored twice either side of Mohamed Salah's temporary equaliser, having earlier missed a penalty, before Raheem Sterling and Phil Foden made certain of a first Anfield win for City since 2003.
Pep Guardiola's men may have conceded for the first time in seven league outings, but the victory was all that mattered - one that moves them five points clear of second-placed Manchester United with a game in hand.
City are unsurprisingly the strong favourites to go on and win a fifth Premier League title in the past decade, and they are also the favourites to win the FA Cup for a seventh time in their history.
However, Swansea are themselves in good form at the moment, sitting one point outside the Championship automatic promotion spots thanks to a run of six wins and two draws in their last eight league outings.
In all competitions, meanwhile, Steve Cooper's side are 10 without defeat, winning eight of those, having also overcome Stevenage and Nottingham Forest in rounds three and four of the FA Cup.
The Swans will perhaps take some inspiration from Man City's fourth-round opponents Cheltenham Town, who led Guardiola's men 1-0 with nine minutes to go of their tie, only to lose 3-1 at Whaddon Road.
It was a similar tale when Man City last faced Swansea in the FA Cup, in fact, as the Citizens were a goal down with 12 minutes to go at the Liberty Stadium, before netting a couple of late goals in a 3-2 win.
Man City went on to win the FA Cup that season and that will be the aim again this time around, with an unprecedented quadruple still on the cards.
This is a competition Guardiola has clearly taken to, having won 18 of his 21 ties. Since the Catalan coach's first season in England, City have scored more FA Cup goals than any other side (65).
Still, this is a competition that has built a reputation down the years for providing big upsets. Swansea, who have reached the quarter-finals in two of the last three seasons, will be looking to add their name to that list with victory on Wednesday.
Swansea City FA Cup form: WW
Swansea City form (all competitions): WWWDWW
Manchester City FA Cup form: WW
Manchester City form (all competitions): WWWWWW
City have been without key man Kevin De Bruyne for the past few weeks and the Belgian playmaker is not expected to return until the end of the month.
Full-back Kyle Walker missed the Liverpool victory through injury but could make his comeback here.
Guardiola has plenty of squad depth to rotate his side, and that is likely to be the case ahead of next weekend's league clash with Tottenham Hotspur.
After rotating his side in the previous rounds, Cooper is expected to go with his strongest available lineup on Wednesday.
That will surely mean a starting spot for Conor Hourihane, who has scored in all three league games since joining on loan from Aston Villa last month.
Swansea City possible starting lineup:
Woodman; Naughton, Cabango, Guehi; Roberts, Hourihane, Dhanda, Grimes, Manning; Lowe, Ayew
Manchester City possible starting lineup:
Steffen; Walker, Garcia, Laporte, Mendy; Fernandinho, Doyle; Mahrez, Silva, Torres; Jesus
We say: Swansea City 0-1 Manchester City
Man City were given a scare by Cheltenham in the last round, but they ultimately got the job done and will feel confident of doing likewise at the Liberty Stadium.
The Citizens have won 12 of their last 14 meetings with Swansea in all competitions, including each of the last six in a row, and we are backing them to prevail on Wednesday.
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