Pep Guardiola's men eased past Swindon Town 4-1 in the third round to make it this far, while their second-tier visitors saw off Bristol City by a goal to nil.
As the old saying goes, anything can happen in football, but it would take a collapse of catastrophic proportions for Man City to lose their grip on the Premier League title now, even if they did drop two points against Southampton in their most recent game.
A Kyle Walker-Peters stunner preceded Aymeric Laporte's equaliser as Man City saw their eight-game winning run across all competitions come to a disappointing end, but they still hold a mammoth nine-point lead over Liverpool having played a game more.
There was no shortage of attacking prowess as City put four past Swindon in the third round of the FA Cup last month, but the passing of the torch may have occurred with Julian Alvarez's capture, as Sergio Aguero's fellow Argentine remains on loan at River Plate for the time being.
Premier League titles and EFL Cup wins are second nature to Guardiola at this point, and while he has only marched to one FA Cup win during his time at the Etihad Stadium, Man City have never been knocked out earlier than the fifth round under his tutelage.
The Premier League champions also welcome Fulham to the Etihad having won each of their last eight on home soil in all competitions, but Fulham ought to be grateful for the practice on City's turf should their promotion bid end up proving successful.
With a late Liverpool deal for teenage sensation Fabio Carvalho collapsing just before the deadline, Fulham can focus all of their efforts back onto their promotion charge with the 19-year-old prospect in tow, as he will certainly expect to be playing Premier League football next term.
Similarly to Man City, Fulham also saw a winning run come to an end courtesy of a 1-1 draw just before the international break, as Aleksandar Mitrovic broke the deadlock after just six minutes against Blackpool before Josh Bowler's equaliser in the second half.
However, Marco Silva's side remain the favourites to finish at the top of the pile and secure an immediate return to the big time following their relegation in 2020-21, with the Cottagers starting the year having scored a whopping 23 goals in their first five Championship games of 2022.
Fulham needed extra time to get the better of Bristol City in the third round of the FA Cup, though, and they have been knocked out in the fourth round two seasons in a row - one of which came at the hands of Man City by four goals to nil in 2019-20.
Six wins and two draws from their last eight away from the home will increase the belief that a shock result could be on the cards, but Fulham have lost their last 11 encounters in all competitions with Man City and are without a goal in this fixture since December 2013.
Riyad Mahrez was granted a week off following Algeria's elimination from the Africa Cup of Nations but should return here, although Ederson and Gabriel Jesus - the latter of whom is not at full fitness - will be late returns from Brazil duty.
Guardiola went surprisingly strong for the trip to Swindon and will likely do so here against the Championship leaders, although Zack Steffen can expect another start in goal after seemingly shaking off a back complaint.
Meanwhile, Fulham are welcome to hand Liverpool loanee Neco Williams his debut for the club this weekend, especially with Denis Odoi securing a move to Club Brugge, and Jean Michael Seri has returned from AFCON duty.
Mitrovic and Harry Wilson both recovered from illnesses to play the full 90 against Blackpool, while Ivan Cavaleiro is fit after a groin problem, but Terence Kongolo and Kenny Tete are both in the medical bay.
Paulo Gazzaniga will aim to displace Marek Rodak in between the sticks for Fulham, as Carvalho continues in the number 10 role behind 28-goal main man Mitrovic. However, Bobby Reid and Antonee Robinson are yet to return from international duty and are absent.
Manchester City possible starting lineup:
Steffen; Walker, Stones, Ake, Cancelo; Gundogan, Fernandinho, Silva; Mahrez, Foden, Grealish
Fulham possible starting lineup:
Gazzaniga; Williams, Ream, Adarabioyo, Bryan; Reed, Cairney; Wilson, Carvalho, Kebano; Mitrovic
We say: Manchester City 3-1 Fulham
Fulham have a taste for goals, Carvalho's rapid rise is showing no signs of showing down, and Mitrovic continues to be unplayable. Those factors may lead to optimism within the Craven Cottage ranks that a famous result at the Etihad is calling.
Silva ought to put out the strongest side possible amid his side's Championship title charge, but a refreshed Man City outfit and their abundance of attacking talent should still prove too strong for the Cottagers' backline.
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