The Reds come into this game with a huge advantage after their dominant second half performance which ultimately saw them 6-2 winners, despite being 2-1 down going into half time.
That game saw Edinson Cavani, Bruno Fernandes and Paul Pogba run the show. United boss Ole Gunnar Solskjær will be hoping for more of the same on Thursday as he looks to reach his first cup final with the club as their manager.
Anthony Elanga has been named in the squad once again, he was also included in the squad that won away at Granada CF in the last round.
For the home side, Goalkeeper Pau Lopez will not play, he dislocated his shoulder in the first leg at Old Trafford. At the weekend Roma were without Leonardo Spinazzola, Jordan Veretout and Amadou Diawara through injury.
A.S. Roma: Mirante; Mancini, Smalling, Ibanez; Karsdorp, Cristante, Villar, Peres; Pellegrini, Mkhitaryan; Dzeko
Manchester United: De Gea; Wan-Bissaka, Lindelof, Maguire, Shaw; McTominay, Fred; Rashford, Fernandes, Pogba; Cavani
Ones to watch
A.S. Roma - Edin Dzeko
Former Manchester City striker Edin Dzeko seems to cause United a problem every time they face him. The Bosnian footballer has played against The Red Devils 10 times, with a 40% win record against them.
However, that's not United's biggest worry. Dzeko has scored eight times and has assisted two other goals when coming up against his former club's rivals, including one in the first leg of this tie.
With nearly 300 club goals to his name, it's clearly known that he's a proven goal scorer. The 35-year-old isn't slowing down either, despite missing a few games this season through injury and because he contracted COVID-19 he's still provided 14 goal contributions in all competitions this campaign.
Manchester United - Edinson Cavani
From one veteran striker to another. Like Dzeko, Cavani was involved in the first leg and was on the score sheet like the Roma striker.
The Uruguayan in fact scored twice. He also set up Fernandes for his first goal and went on to assist Mason Greenwood, who scored the final goal of the game and United's sixth.
Cavani spent three years in Italy when he played for Napoli, but Roma won't need reminding of that. El Matador has played against them 13 times, like Dzeko his win record isn't amazing, with five wins, one draw and seven losses.
However, Roma seem to struggle to stop the 34-year-old from putting the ball into the back of the net whenever they face him. He's scored 13 times against them whilst also picking up three assists.
How to watch and kick off time
The game will kick off on Thursday evening (06/05/21) at 20:00 BST. It will be broadcasted live on BT Sport.