The Red Devils head into the game looking to return to winning ways after the disappointment of their 2-2 draw with Aston Villa in the top flight at the weekend.
Spurs, meanwhile, are enjoying a mini-resurgence following the appointment of Jose Mourinho as their new manager, with Tottenham having won all three of his games in charge so far.
Mourinho is taking his Spurs team to Old Trafford almost exactly a year after he was sacked by the Red Devils as their manager.
The Portuguese coach will be hoping to gain the upper-hand in the race for a top-four finish with victory at Old Trafford against a Manchester United team who have only won four of their 14 games in the Premier League all season.
Former Arsenal star Nicholas believes that the stage is set for a thrilling game when Spurs travel to face the Red Devils in midweek – and he is tipping it to finish 2-2.
Writing in his column for Sky Sports, Nicholas said: “We are all looking forward to it and Wednesday. This is the reason why because this is a stunning game. We have Jose Mourinho’s return to Manchester United to look forward to.
“Will Jose get stick? They didn’t dislike him at Old Trafford. They may not have liked his style and knew deep down that the players went about his ideas the wrong way, mainly Paul Pogba.
“He had problems with Luke Shaw but Jose has always been honest and up front. He did win trophies and got them a Champions League spot so he will not get bombarded.
“I might be wrong but we have a Tottenham team that are three weeks ago would have gone with their heads down – a draw will have delighted them and left them relatively pleased, but Man United are there for the taking if Tottenham want it..
“It is strange how things come up. Tottenham are the favourites at Old Trafford. They do not get results against the big teams, but United nowhere near at the moment.
“I think United will be upbeat for this one as if they have a point to prove, so it will be interesting. Jose will fancy the job though.”
Manchester United are aiming to break back into the top four this season after they finished sixth and without a trophy last term.
They will take on Manchester City in the crunch derby clash at The Etihad on Saturday night.
MORE: Man United latest news
MORE: Arsenal latest news
MORE: Chelsea latest news
MORE: Liverpool latest news