The two sides played out a goalless draw in their initial tie at Molineux earlier this month, setting up another fixture in an already hectic schedule for both clubs.
A draw may always be better than defeat, but a replay is the last thing either of these teams would have wanted to crowbar into their packed fixture lists.
For United this match takes up what was their only free midweek in a month which sees them now play eight times - nine if they make it through - whereas Wolves are already playing their 38th game of the campaign across all competitions.
Ole Gunnar Solskjaer's side will be favourites to progress courtesy of their home advantage, but they will need to show more attacking quality than they did at Molineux, when they failed to register a shot on target for the first time in a domestic game since January 2015.
A chastening EFL Cup semi-final defeat to local rivals Manchester City followed that stalemate, but United finally picked up their first win of 2020 on Saturday, and in some style too.
Marcus Rashford scored twice on his 200th appearance for the club as the Red Devils ran out 4-0 winners over Norwich City, meaning that they have now won 10 and lost just one of their last 15 outings at Old Trafford.
United have not been knocked out in the third round of the FA Cup since 2013-14 and have gone all the way to lift the trophy 12 times, second only to Arsenal in the all-time list.
Indeed, they have reached the final in two of the last four years, although it was Wolves who eliminated them from the competition at the quarter-final stage last season.
If they are to do the same this time around then Nuno Espirito Santo's side will need to end a four-game winless run as they once again go in search of their first victory of the calendar year.
Perhaps unsurprisingly, there have been signs of tiredness creeping in for the team which has played more games than any other Premier League side this season.
Saturday's 1-1 draw at home to Newcastle United saw Nuno's side slip down to seventh in the Premier League table, now eight points adrift of the final Champions League spot, which appears to be up for grabs for any team able to string together a consistent run of form.
Wolves have only made it past the third round of this competition in two of the last eight seasons, although 2018-19 saw them make it all the way to the semi-finals before suffering a heartbreaking defeat to Watford.
United were one of the teams to fall at the hands of Wolves en route to Wembley, of course, and that is part of a five-game unbeaten streak Nuno's side are currently enjoying against the Red Devils - their longest such run since a six-match streak between 1959 and 1962.
Old Trafford has not been such a happy hunting ground, though; Wolves have not won away to United for 40 years, losing eight and drawing two of their 10 visits since then.
Man Utd FA Cup form: D
Man Utd form (all competitions): WWLDLW
Wolves FA Cup form: D
Wolves form (all competitions): WWLLDD
Solskjaer is expected to make changes to his side for this match, with one eye on Sunday's daunting trip to face bitter rivals Liverpool at Anfield.
There will be a balance to strike between rotating and putting out a team strong enough to beat a formidable opponent, though, which means a good chunk of Saturday's team may keep their place.
At the back, Harry Maguire may be given the evening off after defying speculation that he would miss a significant spell with a hip injury, playing the full 90 minutes against Norwich.
Jesse Lingard could be ready to return from illness for the game, while Solskjaer may also take the opportunity to include long-term absentees Eric Bailly and Timothy Fosu-Mensah in his squad to help improve fitness levels.
Nuno is also expected to make some changes to his side as he looks to keep them fresh, although youngster Benny Ashley-Seal may not be in line for another start having been taken off at half time in the initial fixture.
Man Utd possible starting lineup:
Romero; Wan-Bissaka, Lindelof, Jones, Williams; Fred, Matic; Chong, Mata, Lingard; Greenwood
Wolves possible starting lineup:
Ruddy; Dendoncker, Coady, Kilman; Doherty, Saiss, Neves, Vinagre; Traore, Jimenez, Neto
We say: Man Utd 2-1 Wolves
Both teams have bigger fish to fry this season as they chase a European spot in the Premier League and Europa League glory on the continent, but this should still be an intriguing showdown. United will be on a high after their weekend win whereas Wolves have suffered a dip in form since beating Man City, and because of that we are backing the hosts to just edge it.