After 26 matches without a win at the home of the champions Spurs triumphed 3-2 last term, but make the trip carrying injuries to a number of high-profile players.
Rooney - who has scored 11 goals in all competitions for United this season - missed Saturday's 1-0 success at Norwich City with a groin problem but is expected to return for the visit of Tim Sherwood's Spurs.
United's win at Carrow Road was unconvincing, but did mark its sixth successive triumph in all competitions.
Danny Welbeck has scored four goals during that run, and his second-half effort against Norwich was crucial for David Moyes' side, which was missing Rooney and Robin van Persie (thigh).
"I think if we hadn't got so many games and we could give him a couple of weeks just to recover properly, I think [Rooney would] be fine," Moyes told Sky Sports. "But I'd expect him to be OK for the next game against Tottenham.
"Robin has started some light training and he might not be too far away as well. We have not had them as a partnership very often, and we are looking forward to having them together."
While Rooney is likely to be available, Van Persie's problem is expected to keep him out of this match for sixth-placed United.
Also missing are Marouane Fellaini (wrist), Nani (hamstring), Phil Jones (knee) and Rafael (groin), but Antonio Valencia will return from suspension.
Rooney's efforts against Hull City on Boxing Day - where he scored one and set up another as United came from 2-0 down to win 3-2 - were instrumental, and he netted twice in a 2-2 draw at Tottenham earlier this season.
Tottenham made it seven points out of nine under Sherwood in the Premier League with a convincing 3-0 win against Stoke City on Sunday.
The former Spurs midfielder again opted for a 4-4-2 formation and it bore fruit, as Roberto Soldado and Emmanuel Adebayor continued to forge their partnership up front.
Aaron Lennon was excellent once more on the right wing and striker Jermain Defoe (hamstring) could return for Tottenham, which sits seventh in the table.
Paulinho has been ruled out for a month with an ankle injury, while defenders Jan Vertonghen (ankle) and Younes Kaboul (hip) will miss out, as will midfielders Sandro (calf) and Andros Townsend (hamstring). Defender Kyle Walker returns from suspension for Spurs.
Tottenham failed to defeat Manchester United in 26 meetings in all competitions in a frustrating run that spanned almost 14 years.
That ended in September last year, as goals from Gareth Bale and Clint Dempsey helped it to a 3-2 success at Old Trafford - its first since 1989.
The two subsequent clashes have been draws, giving Tottenham hope of a victory that could lift them to it depending on other results.