The cup provides two Premier League heavyweights with their last opportunity to win silverware this season.
Mauricio Pochettino's side reached this stage last year but were beaten 4-2 by London rivals Chelsea, they will be hoping to go at least one step further this time around.
Last chance of silverware
For the Red Devils, it would not mark a very successful season without winning a trophy.
Jose Mourinho's side will be well aware of the demands set by the club's hierarchy and will, therefore, have their sights firmly set on lifting the cup.
However, for Tottenham, as one of the most improved sides in the past decade, the only thing seemingly missing off their record is a trophy.
This year will mark 10 years since they won their last trophy and this weekend will provide them with their last opportunity for the season.
Although, finishing in the top-four would mark a good season for the Lilywhite's, winning a trophy is still what the fans want.
The FA Cup would not turn United's season into a successful one as it is not what the club prioritises as they base their success on the Premier League and Champions League.
But for Spurs winning the cup would mean something totally different, it would break the 10 years without a trophy record and surely set them on their way to further success.
Both sides won their home fixtures when they met in the Premier League, United winning 1-0 at Old Trafford and Spurs winning 2-0 at Wembley.
The sides first met in October 2017 at Old Trafford where United scraped a late 1-0 victory over a Spurs side without Harry Kane.
However, in January Christian Eriksen opened the scoring after only 11 seconds with Phil Jones netting in his own goal to double Spurs' lead.
The two sides have not met in the FA Cup since 2009 where the Red Devils ran out 2-1 winners.
Over the years there have been many incredible games between the two and Saturday's cup clash is set to be another.
Alexis Sanchez only made the bench in United's 2-0 midweek win over AFC Bournemouth but it is not certain that the Chilean will return to the starting line-up on Saturday.
Romelu Lukaku also began the game on the bench, however, the Belgian is fully expected to start in the semi-final.
As for Spurs, Danny Rose remains injured and Kieran Trippier is set to replace Serge Aurier who had another shaky evening at right-back against Brighton.
Toby Alderweireld made his first league start this year and is likely to start after an impressive comeback performance.