Monday's hosts suffered a damaging 3-2 loss to Brighton last week at the Amex Stadium, which increased the pressure on manager Jose Mourinho following a difficult start to his third season in charge of the Red Devils.
Tottenham, on the other hand, have kicked-off their season with two wins from two and could demonstrate their title credentials with a positive result at Old Trafford.
This game is already building up to be one that neither side can afford to lose.
Manchester United 5-2 Tottenham (2009)
Perhaps the most thrilling of encounters between the two sides came in April 2009 when United produced one of their most exciting comebacks to take a big step towards their third straight Premier League title.
They had to do it the hard way, however, as two goals in three minutes from Darren Bent and Luka Modric gave Harry Redknapp's side a comfortable half-time lead at Old Trafford.
However a Cristiano Ronaldo penalty, after a foul by Spurs 'keeper Heurelho Gomes on former Lilywhite Michael Carrick, halved the deficient before the game turned completely on its head. Two goals in the space of a minute from Wayne Rooney and Ronaldo completed the comeback, while the former England captain added a second goal to his name to widen the gap.
A fifth from former Spurs striker Dimitar Berbatov completed the scoring in a thrilling afternoon match in Manchester.
Romelu Lukaku vs Toby Alderweireld and Jan Vertonghen
The trio of players were close teammates during Belgium's World Cup campaign in Russia over the summer, but now Romelu Lukaku will face some familiar faces as the focus turns back to club action.
Toby Alderweireld and Jan Vertonghen have been key cogs in this Tottenham side in recent years, but Lukaku's pace and power will be a problem for them on Monday night. Whoever comes out on top will give their side a key advantage with regards to winning the match.
Manchester United are boosted by the fact that key players Antonio Valencia, Nemanja Matic and Alexis Sanchez all trained this week after suffering various injuries. All three are expected to come into the side as wholesale changes are expected to be made by Jose Mourinho following the Brighton defeat.
Summer signing Diogo Dalot also managed to train this week, but it is believed Monday's match will come to early for the 19-year-old full-back.
Tottenham's main concern this week surrounded goalkeeper and captain Hugo Lloris, who was arrested for drink driving in the early hours of Friday morning. It is widely expected that the Frenchman will not feature for Spurs on Monday night, with Michel Vorm likely to come into the side between the sticks.
Mauricio Pochettino used a 5-3-2 formation against Fulham last week, the same set-up he deployed against Manchester United away last season, so the goalkeeper switch could be the only change in their side from last weekend's fixture.
Manchester United: De Gea; Valencia (c), Bailly, Lindelof, Shaw; Pogba, Matic, Fred; Lingard, Lukaku, Alexis
Tottenham Hotspur: Vorm; Trippier, Alderweireld, Sanchez, Vertonghen, Davies; Dier, Alli, Eriksen; Moura, Kane (c)
Spurs may be higher in confidence than Manchester United, but the north London side have really struggled at Old Trafford in recent years. If Pochettino's side can grab the first goal then they can definitely steer themselves towards three points, but Mourinho has a very good home record against Tottenham in his Premier League career, so expect the form book to go out the window on Monday night.
Predicted Score: Manchester United 1-1 Tottenham Hotspur