Ryan Giggs will be hoping to celebrate his 40th birthday at White Hart Lane, while David Moyes could see both Robin van Persie and Nemanja Vidic return from injury.
It was United's rival Manchester City which sent Andre Villas-Boas' men to a 6-0 defeat last weekend - the club's worst result in the Premier League since a 7-1 loss to Newcastle United in December 1996 - destroying the best defensive record in the English top flight in the process.
A Europa League triumph over Tromso did little to distract from Tottenham's domestic struggles, with consecutive defeats compounded by a persistent inability to find the net.
Tottenham has netted just nine goals in 12 league games - only bottom two Sunderland and Crystal Palace have scored fewer - while United has rediscovered its scoring touch to net as many in its last four league outings.
But it is not all doom and gloom at White Hart Lane, with Tottenham still very much in touch with the top four and, despite the Etihad Stadium capitulation, Villas-Boas' charges still boast more clean sheets [seven] than any other team in the division.
Games against United rarely provide cause for cheer among the Tottenham ranks, though - the London club has not enjoyed a victory on home soil over the Old Trafford outfit since 2001.
The opportunity to achieve that feat twice in a calendar year passed the club by when, in September of the following season, Spurs threw away a three-goal halftime lead to lose 5-3.
Ryan Giggs is one United player who appears to particularly enjoy games against Tottenham, with the Welshman having scored 10 times in matches with Spurs - more than against any other opponent.
The winger turned 40 on Friday and has his sights set on securing a 14th Premier League winner's medal.
Manager David Moyes has paid tribute to the one-club veteran, who has made 953 club appearances since his debut in 1991.
"To be playing so well at his age is terrific and a great example to young players," the Scot said. "We don't look at his age. We look at his experience. He's the right player for this stage."
Moyes' side has turned a corner after a slow start to the campaign with an 11-game unbeaten run, which includes strong form in the Champions League.
The home side, which made nine changes for Thursday's triumph in Norway, could be without Emmanuel Adebayor [groin], while fellow striker Harry Kane [knee], defender Danny Rose [foot] and midfielder Christian Eriksen [ankle] are all sidelined.
Moyes is hopeful that Dutchman Robin van Persie [groin] and defender Nemanja Vidic [head] will return, but midfielder Michael Carrick [Achilles] will miss out.