The Red Devils were beaten 3-1 at home by Paris Saint-Germain to leave their European fate hanging in the balance, but go into this weekend's contest on a run of three successive Premier League wins and a club-record eight away victories on the bounce.
West Ham are also in good form heading into the match, though, and it promises to be a significant occasion regardless of the result as Premier League fans return to a stadium for the first time since March.
Here, Sports Mole looks at how Ole Gunnar Solskjaer could set his side out for the contest.
Manchester United's injury list has shortened dramatically in the last few days, with David de Gea, Alex Telles, Scott McTominay, Paul Pogba, Anthony Martial, Donny van de Beek, Jesse Lingard and Eric Bailly all overcoming doubts to feature in the matchday squad in midweek.
That defeat to PSG did see a different name added to their list, though, with Marcus Rashford forced off 15 minutes from time with a recurrence of a shoulder injury.
Solskjaer remains hopeful that his number 10 will recover in time for this match, but he is unlikely to take any risks over his fitness with a crunch Champions League showdown against RB Leipzig and Manchester derby against Man City to come next week, meaning that Mason Greenwood could come in.
Fred's red card against PSG means that he will miss the trip to Leipzig, making him all the more likely to feature this weekend unless Solskjaer is in the mood to send a message to the Brazilian midfielder.
Luke Shaw is nearing full fitness but this match is likely to come too soon for him, while Edinson Cavani continues to wait for the verdict of an FA investigation into his allegedly racist social media post.
As things stand, the Uruguayan is free to lead the line once again and his match-winning appearance off the bench against Southampton last week - scoring twice and assisting another in a comeback 3-2 win - will surely be enough to earn him another start.
The summer signing has only been on the field for 128 minutes of Premier League action this season but he already has three goals and an assist to his name, directly contributing to a goal every 32 minutes.
That ratio outdoes even Bruno Fernandes, although the Portuguese playmaker could become the first Manchester United player since Denis Law in 1964 to score in six consecutive away league games this weekend.
Man United have won more points per game than any other team in the Premier League since Fernandes's arrival, and have amassed 17 more points in those 23 games than they managed in the 23 immediately prior to signing him.
Watch the Sports Mole Football Shorts prediction for this game below: