The Hammers were thrashed 4-1 at home by Swansea City in one of the shock results of the season on Saturday.
And they can't afford a repeat if they still want to qualify for the Europa League after being leapfrogged by Southampton following their 2-1 win at Tottenham Hotspur.
The big worry for West Ham is that they produced one of the worst performances since Bilic took over in what was such an important game to keep their Champions League hopes alive.
It promises to be an emotional night for all involved on Tuesday as the East Londoners face the Red Devils in the last game ever at Upton Park before the big move to the Olympic Stadium this summer.
And Bilic must make three crucial changes to the side which started against the Swans last time out if he is to get a result against Louis van Gaal's men.
Byram or Tomkins in for Moses
Why Bilic chose to play Chelsea loanee Moses in such an important game given he has only played well on two or three occasions this season left many fans mystified.
Throw in the fact he will be returning to his parent club in the summer and it makes even less sense. He was awful against Swansea and his laziness left makeshift right-back Michail Antonio totally exposed.
He needs to be replaced by either Sam Byram or James Tomkins so they can slot in at right back and allow Antonio to revert to his favoured attacking role, replacing Moses wide right.
Collins in for Reid
How do you solve a problem like Winston Reid? Looked back to his best in recent weeks after a run of indifferent performances but his partnership with Angelo Ogbonna looks fragile.
The pair have conceded over 30 goals in just over 20 games together while in the 11 games James Collins played alongside Ogbonna before his injury the Hammers let in only eight.
Reid and other West Ham players were confronted by angry fans after the Swansea result. The Welsh warrior is the kind of leader the Hammers need for such an important and emotional game.
Sakho in for Carroll
Andy Carroll has been playing well lately but did nothing to prove he should keep the shirt last time out.
Diafra Sakho will cause Manchester United more problems with his pace and power and Carroll makes a better option coming off the bench to exploit tiring defenders.
When Carroll starts it dictates the way West Ham have to play going forward whereas Sakho offers a lot more on his day.