The Red Devils will be looking to bounce back from Wednesday's chastening 2-0 home defeat to Burnley on what is their first ever trip to Prenton Park, whereas Tranmere go into the game off the back of an upset against Watford on Thursday night.
A first home loss at the hands of Burnley since 1962 felt like the final straw for a lot of Manchester United fans, who voiced their displeasure at the way the club has been run in recent years before evacuating Old Trafford in their thousands before full time.
Reports suggest that there are no plans to sack the Norwegian, but he has lost more league games than he has won since his permanent appointment last March and another defeat away to a struggling League One outfit this weekend would pile a huge amount of extra pressure on his shoulders.
It was just a week ago that United were beaten 2-0 by Liverpool on Merseyside and, while that result offered more positives than defeat by the same scoreline against Burnley, it does leave United facing the prospect of losing three games in a row for the first time since April.
The fact that losing to Tranmere is such a realistic possibility speaks volumes about United's current plight, and anything other than victory would only further darken the mood ahead of a difficult run which sees them face Manchester City, Wolverhampton Wanderers and Chelsea in their next three games after this.
Rovers were still a National League team when United made it to the final of this competition two seasons ago, but back-to-back promotions - via the playoffs both times - have lifted the Merseysiders back up to the third tier.
Sixty places still separate these two teams in the football pyramid, though, with Tranmere sitting in the League One relegation zone having won just one of their last 10 league games stretching back to the beginning of November.
Nevertheless, the hosts will go into Sunday's match full of confidence having claimed the scalp of Watford on Thursday night, overcoming their Premier League opposition in extra time after drawing 3-3 in the initial tie at Vicarage Road and then seeing the replay postponed due to a waterlogged pitch.
Watford did field a youthful side showing 11 changes as the Hornets focused on their Premier League survival bid, but it was still a significant result for Tranmere and set up Sunday's money-spinning tie with English football's most decorated club.
Whether facing two Premier League teams in the space of three days proves to be too much for Micky Mellon's men remains to be seen, but they will certainly smell the possibility of an upset considering United's form and their home advantage.
Tranmere FA Cup form: DWWDW
Tranmere form (all competitions): LDLDLW
Man Utd FA Cup form: DW
Man Utd form (all competitions): DLWWLL
The Ivorian is yet to feature this season due to a serious knee injury, but he has been stepping up his fitness in behind-closed-doors matches and could be set for a competitive runout this weekend.
The likes of Paul Pogba, Scott McTominay, Axel Tuanzebe and Marcos Rojo remain sidelined, while Marcus Rashford is also out for the foreseeable future and United are yet to score since his injury was announced.
Both played when United's Under-23 team lost to Tranmere in the EFL Trophy in December, with Chong scoring both of his side's goals, although the uncertainty surrounding his future could play a part in his selection.
Paul Mullin, who scored home and away against Watford including the extra-time winner on Thursday, will hope to have done enough to earn a starting role this time around.
Tranmere possible starting lineup:
Davies; Caprice, Nelson, Monthe, Ridehalgh; Danns, Perkins; Morris, Jennings, Taylor; Mullin
Man Utd possible starting lineup:
Romero; Dalot, Bailly, Lindelof, Shaw; Garner, Matic; Chong, Lingard, Gomes; Greenwood
We say: Tranmere 1-2 Man Utd
A raucous home crowd in a small stadium, a winter-worn pitch and a footballing giant arriving out of form and low on confidence; this match as all of the ingredients of a classic FA Cup upset. Certainly, it looks likely to be a closer affair than the only previous competitive meeting between the two sides, when United won 5-0 in a 1976 League Cup tie.
However, United do still have a significantly better squad and such a quick turnaround for Tranmere against two Premier League clubs could end up hurting them, so we are going for a narrow away victory.