Upton Park was once a bogey ground for the Red Devils; however, the away side arrive in East London with a record of just one defeat in the last six visits, per 11v11.
West Ham can jump two places with victory, and after a disappointing reverse at Stoke City last time out, manager Sam Allardyce will surely be expecting a reaction.
Date: Saturday March 22
Time: 5:30 p.m. GMT/1:30 p.m. ET
Despite enduring an injury-hit campaign for West Ham, striker Andy Carroll will continue his push for a place in Roy Hodgson's England World Cup squad.
Carroll has disappeared from the international picture since a succession of complaints has kept him from playing more than a handful of games at a time for the Hammers.
However, as he showed against Stoke City, a fully fit Andy Carroll is still a handful for most defenders.
Per WhoScored.com, the 25-year-old was West Ham's best player in the game. A 70 percent pass accuracy, combined with five shots on goal and just under half of all headers won, evidenced his threat throughout.
Against Manchester United however, Carroll will need to up his work rate further. Sky Sports' David Jones believes the East London outfit will be facing a transformed United side:
With Nemanja Vidic suspended for the trip, Phil Jones can enhance his own international credentials further alongside ex-Hammer Rio Ferdinand.
Sam Allardyce knows all about Jones' excellence in the central defensive areas, having employed him there whilst manager of Blackburn Rovers.
Sir Alex Ferguson went a step further when asked how good the youngster could be. Per ESPN, he said:
Jones, arguably the way he is looking, could be our best ever player.
I think Jones may be one of the best players we have ever had, not matter where we play him. At 21 years of age, he is going to be a phenomenal player.
I think he can play anywhere on the pitch.
He has such a massive influence, with his instinct and reading of the game. He has a drive about him.
High praise indeed.
Ferdinand may be at the tail end of his own career and has perhaps lost a yard of pace, but West Ham's game hasn't been based on lightning-quick counters since Allardyce's appointment.
If Carroll can get in amongst it from the very first whistle, quickly imposing his natural bullish game, then Kevin Nolan and Mark Noble can prosper from the big man's knockdowns.
At the other end of the pitch, West Ham have to keep things tight to have any hope of piling more misery on Moyes.
Per WhoScored, Rooney particularly excelled just behind the main striker, providing the assist for two of his side's three goals. And the Hammers are one of his favourite victims.
Moyes is acutely aware that unless his side win all nine of their remaining games, United will end up with their lowest-ever points total in Premier League history.
That should be more than enough motivation to see the points head back up the motorway as the Red Devils enjoy something of a late-season renaissance.