Hot on the heels of Sunday's dissapointing reverse at Tottenham, United head to the capital's east end for another crack at the Hammers in the FA Cup.
Anthony Martial's late goal a month ago cancelled out mercurial Frenchman Dimitri Payet's opener to take the two sides back to Upton Park which will host its last ever cup tie with tonight's visit of United.
Coincidentally, West Ham's final Premier League game at their home of 112 years will also be against the Reds in the final week of the season on Tuesday 10th May.
There are no points on offer tonight though, rather a semi-final meeting with Everton at Wembley as the Reds look to end a 12-year itch without winning the famous trophy.
West Ham, meanwhile, are bidding for a fourth success in the competition and a first since 1980.
Slaven Bilic's side are enjoying a good season, sitting sixth in the Premier League with a strong chance of European football and targeting the FA Cup as a realistic hope of silverware.
Tim Fosu-Mensah impressed in his 68 minutes against Spurs but was forced off through injury so his fitness is unknown but Wayne Rooney played an hour for the Under-21s so could feature.
Phil Jones was also included in that match and may come back in, but the hosts will be without Diafra Sakho, Alex Song, Sam Byram, James Collins and Carl Jenkinson.
United manager Louis van Gaal:
"The FA Cup is our last chance of a trophy so it is very important for the players, for the club, me as the manager and, of course, the fans.
"We did not win against West Ham at home so now we have to play them again, this time away, and we have had one day less to prepare so I hope that does not affect us.
"It shall be different from a league game because if you lose the game you are out and then you cannot win.
"West Ham are difficult opponents and I saw against Arsenal the 'Andy Carroll show' but they have other players who are dangerous also- Payet for example and Lanzini can also score and create goals so we know that is shall not be easy but hopefully we can continue." said the Dutchman.
The two sides have already met twice this season- both times at Old Trafford and both ended all square (0-0 in the league in December and then the first installment of the tie a month ago).
Form guide: West Ham W W D D D D United L D D W W L
Match odds: West Ham 17/10 United 9/5 The match to be decided on penalties 11/4
Referee: Roger East