The league meetings between the sides this season were split, with United winning 1-0 at Old Trafford in October and Spurs triumphing 2-0 at Wembley in January.
Mauricio Pochettino's side are playing in the stadium where they have been contesting all their home matches this season, which might give them a slight advantage.
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Phil Jones and Daley Blind remain the only injury concerns for Jose Mourinho, who rotated in his side's 2-0 win at Bournemouth on Wednesday night.
For Spurs, Harry Winks remains sidelined, while Toby Alderweireld returned from three months out in midweek.
Goals at a premium at Wembley
Spurs have played 16 league games at Wembley this season and kept eight clean sheets, including against United when Christian Eriksen scored after 11 seconds.
Mourinho's men, though, have the second-best defensive record in the top flight and the Portuguese is notoriously effective at keeping things tight in big matches.
The Red Devils will have no problem in trying to frustrate Spurs, and this should lead to a another low-scoring match.
Tips and predictions
Under 2.5 goals in the game is priced at 3/4 (1.75) and looks like a strong selection.
This bet paid out comfortably in both league meetings this season, as well as in five of their last eight clashes.
With plenty on the line for both sides, another tight game seems almost guaranteed on Saturday.