Wednesday go into the clash with the reigning champions off the back of a disappointing 3-1 home defeat to Derby County in the Championship at the weekend.
Despite failing to emulate the success of their last two Premier League campaigns, City continue to assert their dominance in the domestic cup scene, and have now won four on the bounce in all competitions following Sunday's 2-1 win over Aston Villa at Wembley.
Nevertheless, the manner of City's victory was certainly less emphatic than we've become accustomed to seeing from Pep Guardiola's side in cup finals, most notably their 6-0 thrashing of Watford in last season's FA Cup final.
A two-year ban from European football has done little to damage the spirit and tenacity of Guardiola's players. The Sky Blues' 2-1 victory over Real Madrid at the Bernabeu will live long in the hearts of the Etihad faithful, who will no doubt start to believe that a European crown could await their side come the end of the season.
Guardiola himself has admitted that his reign in the Etihad dugout would be a failure without a Champions League trophy to his name, but the Spaniard's focus must now turn to Hillsborough for City's first meeting with Wednesday since 2015.
The Citizens cruised to victories over Port Vale and Fulham to reach the fifth round, and are now facing a side whom they haven't lost to since 1993. James Milner's double gave City a 2-1 win in the last match between the two sides in the third round of the 2014-15 competition.
In contrast, Wednesday lie smack-bang in the middle of the Championship table, but have seen their playoff hopes dwindle in recent weeks with only one win in their last six.
The Owls conceded three goals in the opening 30 minutes as they fell to defeat against Derby in front of the Hillsborough faithful on Saturday, meaning the pressure continues to pile on manager Garry Monk.
Wednesday's 1-0 victory against Charlton was their first win since Monk's side overcame Queens Park Rangers in the fourth round of the FA Cup, and the Owls will be expecting a strenuous battle against the Citizens as they look to advance past the fifth round for the first time since 1999.
It has been 85 years since Wednesday last tasted FA Cup glory, defeating West Bromwich Albion 4-2 in the 1934-35 final. The three-time winners last reached the final in 1993, holding Arsenal to a 1-1 draw before losing 2-1 in the replay after extra time.
Sheffield Wednesday FA Cup form: WW
Sheffield Wednesday form (all competitions): DLLDWL
Manchester City FA Cup form: WW
Manchester City form (all competitions): LLWWWW
Guardiola is expected to make several changes to the side that beat Villa on Sunday.
Sergio Aguero was substituted after picking up a knock in Sunday's final, however the South American has confirmed that the injury is not serious.
Joao Cancelo missed out altogether against Villa, but has played every minute of City's FA Cup campaign this season thus far. Kevin De Bruyne, Riyad Mahrez and Gabriel Jesus all started Sunday's final on the bench and will be eyeing up a place in the starting XI come Wednesday.
The Owls have no fresh injury concerns going into the fifth-round clash.
Top scorer Steven Fletcher lasted only 45 minutes on his first-team return against Derby, however Monk affirmed that the Scotsman's substitution was only a precautionary measure.
Sheffield Wednesday possible starting lineup:
Dawson; Palmer, Lees, Iorfa, Fox; Murphy, Bannan, Lee, Windass; Fletcher, Wickham
Manchester City possible starting lineup:
Bravo; Cancelo, Otamendi, Garcia, Mendy; Rodri, De Bruyne, Gundogan; Mahrez, Jesus, B Silva
We say: Sheffield Wednesday 0-3 Manchester City
Guardiola's side have not suffered defeat in the FA Cup since February 2018, and we're backing them to continue that remarkable run with a comfortable victory against an out-of-sorts Wednesday side.