Vale make the short trip to the Etihad Stadium sitting in 10th position in the League Two standings, meaning that 76 places separate the clubs in the English pyramid.
At the start of the season, winning the FA Cup would have been third on Pep Guardiola's list of priorities, behind defending the Premier League title and lifting the Champions League for the first time in the club's history.
However, with claiming another top-flight crown becoming increasing unlikely, Guardiola will be more focused on trying to successfully defend the trophy that they won with a 6-0 demolition of Watford at the end of the last campaign.
After a hectic Christmas and New Year period and ahead of the first leg of their EFL Cup semi-final with Manchester United, facing one of the lowest-ranked teams left in the competition at the Etihad Stadium is the perfect draw for City.
Guardiola will naturally rotate his squad, likely leaving plenty of the players who started the 2-1 win over Everton on New Year's Day on the sidelines.
However, after seeing his minutes restricted through injury and the form of Gabriel Jesus, Sergio Aguero will be looking to take his frustration out on City's next opponents as he bids to reclaim his place in the team.
As for Vale, they make the daunting trip to the Etihad having put together a five-match unbeaten streak since the middle of December.
Despite four of those outings ending in draws, avoiding defeat during a busy schedule should provide John Askey's team with plenty of belief ahead of their visit to one of the biggest clubs in Europe.
The Staffordshire outfit have come through two difficult fixtures in order to reach the last 64, with victories being achieved on the road against MK Dons and Cheltenham Town respectively.
Building on 10th spot in League Two will be the priority for the rest of the season but for now at least, Askey and his players deserve to enjoy testing themselves in unfamiliar surroundings.
Manchester City form (all competitions): WWWLWW
Port Vale FA Cup form: WW
Port Vale form (all competitions): LDDDWD
Aguero is a likely starter on Saturday evening, and the Argentine may be joined by Raheem Sterling, who only featured as a late substitute against the Toffees.
Vale boss Askey must decide whether to make any alterations to the side that claimed a 2-2 draw with Macclesfield Town earlier this week.
David Amoo, a former Liverpool trainee who made one senior start for the Merseyside giants in a Europa League qualifier, is expected to feature on the flank.
Manchester City possible starting lineup:
Bravo; Walker, Garcia, Harwood-Bellis, Angelino; Doyle, D.Silva; Sterling, Bernabe, Zinchenko; Aguero
Port Vale possible starting lineup:
Brown; Gibbons, Legge, Smith, Montano; Taylor, Joyce, Burgess; Amoo, Bennett, Worrall
We say: Manchester City 5-0 Port Vale
While City will likely make mass alterations, we cannot see anything other than a routine victory over the Premier League giants. Vale will fancy their chances of a consolation goal, although much could depend on how they last the pace.
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