The Red Devils have endured a week to forget so far, as they suffered back-to-back 2-0 losses against Liverpool and Burnley in the Premier League. It will be fascinating to see what team manager Ole Gunnar Solskjaer selects for this encounter as he looks to stop the rot.
Tranmere will feel they can cause an upset. The third-tier team beat a much-changed Watford on Thursday to set up this fixture and will look to exploit some vulnerabilities in the United setup.
Here are the latest odds for the match at Prenton Park, as well as the key viewing details and a preview.
Tranmere win (6/1)
Manchester United win (2/5)
Odds courtesy of Caesars
Date: Sunday, January 26
Time: 3 p.m. (GMT), 10 a.m. (ET)
TV Info: BT Sport 1 (UK)
Both United and Tranmere needed to win replays to get to this stage of the competition, although the mood in each camp will be very different going into Sunday's game.
The Red Devils have slipped into a crisis after successive losses in the Premier League. While a defeat to Premier League leaders Liverpool wasn't a huge shock, the slip against Burnley and the manner of the team's performance was cause for serious concern.
Solskjaer has unsurprisingly come in for some flak, and Miguel Delaney of The Independent questioned the club's decision to appoint him:
However, the manager has said that turning United's fortunes around will not be an easy task:
Given recent results and the fact Sunday's game is an FA Cup clash, it seems likely Solskjaer will freshen up his side for the Tranmere game.
One man the supporters will want to see come into the side is Mason Greenwood, with the young forward one of a few bright spots in what has been an underwhelming season so far.
He's been able to showcase his potency in front of goal:
It will be a difficult ask for Tranmere to stop him, but the League One side will feel capable of causing problems for their visitors.
There's clearly a huge amount of spirit in Micky Mellon's side. In the previous round, they recovered from three goals down to draw 3-3 with Watford and then beat them 2-1 in the replay on Merseyside in extra time.
Here is the moment Paul Mullin headed Rovers into the fourth round:
One obstacle United will have to deal with at Prenton Park is the playing surface. Per Mark Ogden of ESPN, the Red Devils are unlikely to have played on a pitch like Tranmere's this term:
While Tranmere will be determined and backed by a fervent crowd, playing 120 minutes on Thursday on such a cut-up surface will have taken a lot out of them. On Sunday, they will likely be chasing the ball for long periods and legs could become heavy quickly.
United may have to weather a storm in the opening stages, with Tranmere likely to test them out with long balls into the channels and crosses into the box. In the end, the Premier League side will surely have a little too much for their third-tier opponents.
Prediction: Tranmere 0-2 Manchester United