The Red Devils have been utterly dominant in the Europa League so far, having thoroughly beaten Real Sociedad by a scoreline of 4-0 and getting the better of AC Milan at San Siro. They've kept five clean sheets in their six games so far, conceding just one goal.
The Giallorossi have been impressive as well, getting past the likes of Shakhtar Donetsk and Ajax in the knockout rounds. They have the highest scorer in the competition, Borja Mayoral, and two Roma players in Henrikh Mkhitaryan and Chris Smalling could be set to face their former clubs in the semi-final tie.
The pair won the Europa League with Manchester United in 2017, when Jose Mourinho led the Red Devils to their first and only UEL title with a win against Ajax. Only four players who are likely to start for Solskjaer's side were present in the side during their win.
Ahead of the fixture, here are five key battles that could define the outcome of the tie.
Manchester United v Roma: 5 Key Battles
#5 Rick Karsdorp vs Luke Shaw
Luke Shaw has been one of the most in-form defenders in world football over the course of the season and will undoubtedly be one of Manchester United's main threats in the semi-final tie. The Englishman has created more chances than any player in the Premier League so far and has been an immense attacking outlet on the Red Devils' left side.
He will come up against Rick Karsdorp on his side of the pitch, which could be a fascinating battle to watch out for.
The Dutch full-back had a slow start to life in Rome but has impressed profoundly in Paulo Fonseca's 3-4-2-1 system as a wide defender, and he will have to be at his best to nullify Shaw's menacing runs into Roma's half during the game.
#4 Lorenzo Pellegrini vs Scott McTominay
Roma captain Lorenzo Pellegrini has been one of the most impressive Giallorossi stars under Fonseca and will be a player Manchester United need to keep in check during the tie. The Italian is an imposing figure who has been given the license to run at defences, which Scott McTominay will have to prevent. Pellegrini averages more chances created (2.15) than any Roma player this season.
McTominay has already shown in the past that he's capable of shutting down midfielders and, in the process, limiting the opposition's attacking threats.
The Scot will lock horns with the Roman club's skipper, which will not be an easy task for him, and a lot of Roma's attacking play will depend on how well McTominay can contain Pellegrini.
#3 Roger Ibanez vs Paul Pogba
Paul Pogba has reinvented himself in recent months by playing on the left of a midfield three players behind the striker. He's been a joy to watch, taking on players for fun and pulling the strings in the final third. He has, more often than not, provided the killer pass to unlock defences. Pogba's displays against Tottenham Hotspur and AC Milan have been prime examples of this new role.
Against Roma, the onus of keeping Pogba at arm's length is likely to be placed on young Roger Ibanez. The 22-year-old Brazilian has been in fantastic form this season and has garnered attention from Liverpool with his displays.
Ibanez could start on the right side of Roma's three-man defence and end up facing Pogba. The majestic Frenchman will prove to be a tricky test for the South American.
#2 Chris Smalling vs Edinson Cavani
After nearly a decade of service at Old Trafford, Manchester United's Chris Smalling has found a new lease of life with the Giallorossi. Smalling initially moved on a loan deal and has gone on to become a titan in defence for Roma, who were impressed with the Englishman and made his move permanent. Smalling will be tasked with keeping out one of the best strikers of his generation, Edinson Cavani.
The Uruguayan has been in superb form over the last few weeks, scoring the winners against Spurs and Granada and capping off a slick team move against Burnley.
Cavani is one of the best headers of the ball in Europe and will be a handful for Smalling to deal with. The 34-year-old has scored more goals against Roma than any other Italian side (nine) in his career.
#1 Edin Dzeko vs Harry Maguire
Arguably the biggest and most influential battle of the night could be that between Harry Maguire and Edin Dzeko. The Manchester United captain has been a colossus for the Red Devils, helping them keep four clean sheets in the five UEL games he's played. Maguire has been in sublime touch, particularly in 2021, and will be the main player responsible for dealing with Edin Dzeko.
The former Manchester City striker has an abundance of experience playing against the Red Devils as he's scored six goals against them in his career.
Dzeko already has four goals and an assist in the Europa League this season, and Solskjaer has already spoken about the Bosnian's threat, saying "any ball in the box is a dangerous one."
Maguire will have to be at his sharpest, both on the ground and aerially, to stop Dzeko from influencing the semi-final tie.