Fulham pulled off an upset by knocking out Aston Villa in the last round, but they have lost their last eight matches against City in all competitions.
City have lacked consistency in the Premier League this term but have been as ruthless as ever in the domestic cup competitions.
Pep Guardiola's men lifted the EFL Cup and FA Cup last season, as well as the Premier League, and are on course to retain both cups.
Having opened up a 3-1 first-leg lead over Manchester United in the EFL Cup, focus now turns to the visit of Fulham on Sunday and Guardiola has indicated he will field a strong XI.
The domestic cups and Champions League will take on added importance for the Citizens in the remaining months of the campaign due to their patchy league form, which has seen them all but relinquish their grip on the title.
A 2-2 home draw with Crystal Palace aside, City's form over the past month has been impressive as they have won six of their last seven games in all competitions.
That includes a 4-1 win over Port Vale in round three, with four different goalscorers registering at the Etihad Stadium to make it seven FA Cup wins in a row for City.
Fulham are the latest side with aspirations of stopping the reigning English champions, and they have already eliminated one Premier League club in Aston Villa this season.
Not since 2002-03 have they knocked out two top-flight sides in the same FA Cup campaign, however, and Scott Parker's charges enter the match on the back of a disappointing goalless draw at Charlton Athletic in midweek.
The Cottagers' failure to find a way through at The Valley means they remain three points adrift of the automatic promotion spots after playing a game more than the top two.
Earning a place in the Premier League remains the top priority for Parker, but this trip to the Etihad Stadium will be seen as a welcome distraction and a chance to pull off a massive upset.
Manchester City's FA Cup form: W
Manchester City's form (all competitions): WWWWDW
Fulham's FA Cup form: W
Fulham's form (all competitions): WLWWWD
Aymeric Laporte made a shock return to City's starting lineup against Sheffield United, coinciding with the club's first clean sheet in six matches.
The Frenchman, described as the best defender in the world by Guardiola, is expected to be eased back in after five months out so he could be given a day off on Sunday.
Young defenders Eric Garcia and Taylor Harwood-Bellis are pushing for inclusion, as is cup regular Phil Foden, who has been directly involved in nine goals in eight appearances against lower-league opposition.
As for Fulham, Aleksandar Mitrovic has spent a spell on the sidelines and is out for at least another week, but Parker's injury concerns have otherwise cleared up.
Manchester City possible starting lineup:
Bravo; Cancelo, Stones, Garcia, Zinchenko; D.Silva, Gundogan, Foden; Bernardo, Aguero, Sterling
Fulham possible starting lineup:
Rodak; Christie, Hector, Mawson, Odoi; Arter, Onomah, McDonald, Cairney; Cavaleiro, Reid
We say: Manchester City 3-0 Fulham
Man City have scored 30 goals and conceded only four since last tasting defeat in the FA Cup just under two years ago. Guardiola is expected to field a strong side and that could spell trouble for Fulham, who have lacked goals in the absence of leading marksman Mitrovic.