Just three places separate the sides in the Premier League in what is arguably the pick of the sixth-round ties, though United head into the match as firm favourites.
Having come within a couple of minutes of pulling off the ultimate smash-and-grab away at Chelsea last weekend, Wolves will have their sights set on stifling another top-six giant in Saturday evening's clash at Molineux.
Wolves have built a reputation for bloodying the noses of the country's best sides - a category they only just fall outside of by virtue of their seventh-placed standing in the Premier League.
Nuno Espirito Santo's men are on course to finish best of the rest in the top flight, sitting a point better off than Watford and five in front of West Ham United with eight games of their league campaign to go.
Finishing seventh would be a great achievement for the West Midlands outfit in their first campaign back in the big time, of course, yet there is a sense that this is just the start. Coupling that seventh-place finish with a first FA Cup semi-final appearance since 1997-98 would be a good way to lay down a marker for sustained success.
That is now ultimately the goal for Nuno, who has impressed during his time in English football so much - so that he has already been touted as a managerial target for Chelsea and this weekend's opponents Man United, albeit before Ole Gunnar Solskjaer turned the latter's fortunes around.
Nuno had to defend his tactics on the back of last weekend's 1-1 draw with Chelsea, having seen his side score from just one of two shots all afternoon - an impressive breakaway goal rounded off by Raul Jimenez, who can be pleased with his debut campaign at Molineux.
Wolves did what they had to to come away from Stamford Bridge with a positive result, picking up their 10th point against a big-six club this season - at least two more than any team outside of the division's elite - to keep them on course for European football next season.
One of those points came against United at Old Trafford in October so, with home advantage in this latest tussle, Wolves will be looking to claim another scalp and make it three consecutive FA Cup victories for the first time since February 2003.
Liverpool have already fallen at Molineux in this season's competition, as have Shrewsbury Town in a fourth-round replay before Wolves held off Bristol City 1-0 last time out. It sets them up nicely for what could yet be the highlight of a campaign to remember, and a trip down Wembley Way.
Recent form in FA Cup: WDWW
Recent form (all competitions): DWDLWD
For the first time in Solskjaer's three-month tenure, United tasted defeat in the Premier League last Sunday as they lost 2-0 away to top-four rivals Arsenal.
It could well prove to be a massive blow in their hopes of playing Champions League football next term, though a two-point gap on fourth place is something the Red Devils would happily have accepted when 11 points adrift in mid-December.
Solskjaer's record still reads an impressive 14 wins, two draws and two defeats from 18 matches in all competitions. As well as lifting United into top-four contention, the Norwegian has also guided the club into the quarter-finals of the Champions League and FA Cup.
Last week's memorable and historic 3-1 win at Paris Saint-Germain may well have been the result that leads to Solskjaer being named United's permanent boss in the coming weeks, seeing them through to the last eight of the European Cup along with three other English clubs.
The FA Cup also provides Solskjaer with a chance to win some silverware, though, and having lifted it a couple of times before as a player he knows just how much the competition means to supporters. For a club of United's stature, lifting the famous trophy just a couple of times this millennium is a shocking return.
Not since 2005 under the watch of legendary boss Sir Alex Ferguson have the Red Devils made it to the semi-finals in consecutive seasons, which they can achieve with victory on Saturday after making it all the way to the final last time out, where they were beaten by Chelsea.
Season-defining it may not be, but this trip to the West Midlands now becomes a little more important for Solskjaer on the back of his side's defeat at the Emirates Stadium. Heading into the international break on the back of successive losses is never good, especially when discussing terms for a new deal.
United boast an impressive record away from home in the FA Cup, though, winning nine of their last 10 - losing the other to Chelsea at this stage in 2016-17 - and in Solskjaer they have a manager with a 100% away record in the competition, winning twice on his travels with Cardiff City and twice this season with the Red Devils.
Maintain that run on Saturday and nobody will doubt that he is the right man for the job.
Recent form in FA Cup: WWW
Recent form (all competitions): WDWWWL
Solskjaer does not have the luxury of being able to rotate his side too heavily, mainly because he is still without a number of first-team players but also because Wolves are too strong an opponent to take risks against.
Anthony Martial and Nemanja Matic made their return to action against Arsenal last weekend and are in contention to start here, though Scott McTominay has done well of late and gives his manager an extra option in the engine room.
In terms of the hosts, they incredibly have a fully-fit squad to choose from at this stage of the season, leading to Nuno joking last week that he will send his medical staff away on holiday until the summer.
Ryan Bennett is serving a two-match ban after collecting 10 yellow cards, but that only applies to the Premier League so he will likely return from the 1-1 draw with Chelsea in place of Romain Saiss, who can slot into defensive midfield.
Fellow defender Matt Doherty has been involved in more FA Cup goals than any other player among the teams left in the competition - five, three of those being goals of his own, as well as chipping in with a couple of assists.
Wolverhampton Wanderers possible starting lineup:
Ruddy; Bennett, Coady, Boly; Doherty, Dendoncker, Saiss, Neves, Vinagre; Jimenez, Jota
Manchester United possible starting lineup:
Romero; Dalot, Jones, Bailly, Shaw; Fred, McTominay, Pogba; Rashford, Lukaku, Martial
Head To Head
Of the previous 99 meetings between these two sides, Wolves have won 34 and lost 48, including eight defeats in the last 10 encounters.
The sides last met in the FA Cup 13 years ago when United claimed a 3-0 victory at Molineux to progress through to the fifth round.
We say: Wolves 1-1 Man United (United through on pens)
United have already defeated Arsenal and Chelsea away in this season's FA Cup so this is a test, even if Wolves do boast a good record against teams of United's calibre, that the visitors should pass. With no replays, though, we are expecting Solskjaer's men to do things the hard way.