United head into the game having been beaten 2-0 by Liverpool on Thursday night, and the pressure is back on manager Louis van Gaal after that torrid Europa League defeat.
The FA Cup may be United's best and final chance of winning silverware this season, but they are faced with a tough task against a buoyant West Ham side.
Slaven Bilic's men came from 2-0 down to beat Everton 3-0 last weekend, and that came after successive 1-0 wins over Sunderland and Tottenham Hotspur.
Now fifth and just two points off the top four, West Ham may be on the verge of major success in the Premier League, and will be hoping to reach the semi-finals of the FA Cup on Sunday afternoon.
Pundit Mark Lawrenson has now had his say on the game, and Hammers fans may in fact be delighted with his somewhat surprising prediction, given his usually negative predictions for West Ham this season and their difficult trip to Old Trafford.
Lawrenson told BBC Sport that he thinks West Ham will earn a 1-1 draw at Old Trafford on Sunday afternoon, and then beat the Red Devils in the replay at Upton Park, as he praised the club's recent form, and suggested they won't get bullied away from home.
"This is going to be a tough one for Manchester United because West Ham are on a roll at the moment," said Lawrenson. "The Hammers do not let teams bully them away from home and they are great at coming from behind in games. They can take the tie back to Upton Park - and I fancy them to win it there," he added.
What's your prediction for Manchester United v West Ham United?