Pep Guardiola's side have been relentless lately, winning their last nine games and going unbeaten in 16, stretching all the way back to November last year.
During that period, they also dispatched Birmingham City 3-0 in the last round of this competition and are widely expected to extend their winning streak further.
Cheltenham, the clear underdogs in this duel, have never beaten a Premier League side in eight previous attempts in the FA Cup. It is fair to say that they have a Herculean task on their hands.
The Robins won't feel too inspired by their recent record either, winning just once from their last nine games in all competitions.
That victory came in the last round of the competition when they saw off their League Two rivals Mansfield Town 2-1 in extra time.
Cheltenham vs Manchester City Head-To-Head
This will be the first ever competitive meeting between the sides.
Cheltenham Form Guide (all competitions): D-D-W-D-D
Manchester City Form Guide (all competitions): W-W-W-W-W
Cheltenham vs Manchester City Team News
Chris Hussey sustained an injury against Newport County on Wednesday and will be sidelined, while Elliot Bonds is also set to miss out. However, Sean Long is back in the squad and will be available for selection.
Injured: Chris Hussey and Elliot Bonds
Sergio Aguero tested positive for COVID-19 and will hence miss the clash. Meanwhile, Aymeric Laporte has been sidelined since the start of the month.
As much as Guardiola takes all competitions seriously, we expect him to make wholesale changes to his lineup, with most of the first-team stars rested.
Injured: Aymeric Laporte
Unavailable: Sergio Aguero
Cheltenham vs Manchester City Predicted XI
Cheltenham (3-5-2): Joshua Griffiths; Charlie Raglan, Ben Tozer, William Boyle; Matty Blair, Chris Clements, Finn Azaz, Liam Sercombe, Lewis Freestone; George Lloyd, Alfie May.
Manchester City (4-3-3): Zack Steffen; Joao Cancelo, Taylor Harwood-Bellis, John Stones, Benjamin Mendy; Tommy Doyle, Fernandinho, Bernardo Silva; Ferran Torres, Gabriel Jesus, Cole Palmer.
Cheltenham vs Manchester City Prediction
Despite all the changes that Guardiola is set to make, City will still have enough in the tank to cruise towards another routine win.
Prediction: Cheltenham 0-4 Manchester City