The game will be the fourth in the space of a week for Spurs and eighth in the last 22 days, but they go into it having coped with the schedule better than they might have expected.
Spurs have knocked Chelsea out of the EFL Cup and progressed to the Europa League group stages with a 7-2 win over Maccabi Haifa in their last two outings, so will be full of confidence against a United side searching for their first home win of the campaign.
Here, Sports Mole looks at how Mourinho could line his side up for the contest.
Mourinho has refused to completely rule Son out of this match, but admitted that it would be a "surprise" if the forward recovered in time after being forced off at half time last weekend.
In all likelihood Spurs will be without the Korean, while Giovani Lo Celso also looks set to miss this one after feeling tightness in his muscle against Maccabi Haifa on Thursday.
The Argentine scored twice before his half-time withdrawal and, while the injury is not thought to be serious, the relentless schedule means that Mourinho is unlikely to take any risks over his fitness.
Muscle tightness is to be expected after such a brutal run of games, but Spurs may be relieved that they have got through that period relatively unscathed - especially considering the injury woes they faced last season.
The one guaranteed injury absentee is long-time Man United target Gareth Bale, who will have to wait until after the international break for his second debut for Spurs, but their newest arrival Carlos Vinicius is ineligible to play having only signed on Friday evening.
Dele Alli's future has been cast into doubt due to his recent omission from squads and, ordinarily, he may not have taken part in this match, but the injury concern over Lo Celso and need to keep players fresh could force Mourinho's hand.
The manager has praised Alli's professionalism recently and appeared to hand him a lifeline when he replaced Lo Celso off the bench on Thursday, eventually scoring from the spot on his return to the team.
Harry Kane will lead the line looking to add to both his hat-trick from Thursday and tally of five top-flight assists already this season - a joint-Premier League record after three games of a campaign.
The England skipper has only scored twice in 12 Premier League games against Manchester United, though, so will be out to improve that record.
Watch the Sports Mole Football Shorts prediction for this game below: