Erik ten Hag is expected to give several of his fringe players the chance to shine as United welcome Nottingham Forest to Old Trafford.
Barring a cataclysmic catastrophe, the Reds will face Newcastle at Wembley on 26 March as we hold a three-goal advantage from the first leg; no side has ever recovered from such a deficit and - with United unbeaten at home since September - the odds are firmly weighted in favour of ten Hag's side.
This game presents an ideal opportunity to rotate and give youth a run-out but will ten Hag continue with his tendency to select strong sides?
With that in mind, and with the team in the middle of a hectic run of fixtures, here is how we think the Reds will line up at OT this evening.
In goal, David de Gea is likely to be given the night off so expect either Tom Heaton or Jack Butland to get the nod. We think the on-loan Palace keeper Jack Butland is set to make his debut. Why bother signing him if you don't play him in games like this? It will certainly be a night to cherish for either one of United's back up stoppers to get a rare chance to play in a semi final under the lights at Old Trafford.
Butland will line up behind a defence of Aaron Wan - Bissaka, Raphael Varane, Harry Maguire and Brandon Williams.
Diogo Dalot is still sidelined so AWB will continue his run of games. It's possible Williams plays at right-back with Tyrell Malacia on the left, but there is no reason to think ten Hag will give AWB a breather. He has been good recently and so starts in our predicted side.
It might seem unwise to risk injury when the tie is already won, but Varane has been rotated out for the first leg of this one and the cup tie with Reading. Varane will play against Palace on Saturday but we don't want him going into it with no minutes for a fortnight, so it makes sense to start with the Frenchman here.
Alongside him, the skipper gets another 90 minutes under his belt having come in from the cold to perform well against Championship opposition.
Luke Shaw is still absent and Malacia needs a rest, so Williams is set for his first start of the season at left-back. As mentioned, he could fill in for AWB at right-back with the young Dutchman in his stead but we think Malacia will get the night off.
In front of them, our options are limited. Scott McTominay and Christian Eriksen are injured and Casemiro needs a rest. Fred is almost a certainty to start after impressing from the bench of late, with teenager Kobbie Mainoo to be handed a second senior start. Mainoo played against Charlton in the quarter-finals and ten Hag is a keen admirer so there's no reason why he shouldn't be in from the start again for this one.
Facundo Pellistri has impressed me in his fleeting, two-game cameos so far so I'd really like to see him in from the start. Jadon Sancho will return to the squad but is likely to be on the bench after three months out and Antony will also be rested. That paves the way for the talented young Argentine to step in lieu of his more established senior colleagues.
With Bruno Fernandes rested and no one else to come in, 19-year-old Zidane Iqbal comes in for his first senior start. His only first-team appearance so far came in the last minute of last season's dead rubber group stage match with Young Boys but the Old Trafford stage is calling for United's first-ever British-born South Asian.
On the left, Anthony Elanga failed to secure a loan move during the transfer window despite a whole host of clubs scrapping for his signature. The Swede will be a valuable squad player for United under ten Hag and should get a rare chance to impress his manager here.
Up top, Alejandro Garnacho is due a run-out and with Anthony Martial set to be on the bench, Wout Weghorst can also be rested to allow the young Argentine a start.
So there we have it: a rotated Reds side focused on youth but, with an unassailable lead already, it's the perfect time to give our senior men a long-awaited and much-needed breather.