When: Sunday April 11, 16:30 GMT
How to watch: Sky Sports Main Event
Despite the 6-1 thrashing back in October, the bookies will favour Manchester United for this fixture - irrespective of this however, the Red Devils will face a tough test in a Tottenham side determined to save their season by securing Champions League football once again.
Of the six goals scored by Edinson Cavani in 19 Premier League appearances, four of the Uruguayan's efforts have come from headers.
Initially dividing fans and pundits alike, Tanguy Ndombele has been somewhat of a revelation at the Tottenham Hotspur Stadium this season, lauded for his creativity and diverse range of passing capabilities.
Jose must spur Tottenham towards Champions League challenge
Following that aforementioned 6-1 away victory at Manchester United in the fourth game of this current Premier League season, Tottenham embarked on an untouchable run of form in the fixtures that followed - a run that would see them top of the league after a comfortable 2-0 victory over Manchester City in late November.
With this in mind, it will come as no surprise that five months on from their promising early showings, the general feel surrounding the Tottenham Hotspur Stadium at the moment is that Jose Mourinho's men have been somewhat underwhelming in the second half of the season thus far.
Sitting sixth in the Premier League with stiff competition from a revitalised Chelsea and high-flying West Ham for the final Champions League place, and with a daunting Carabao Cup final against a dynamic Pep Guardiola side being their only hope of silverware - following their calamitous exit from the Europa League - Mourinho faces an uphill battle to salvage their season.
With Champions League football being regularly guaranteed under Mauricio Pochettino and the Argentine inspiring his side to a Champions League final in 2019, many viewed the dismissal of Mourinho's predecessor as unjust - and should Spurs endure a trophyless season in which they finish outside the top four, the ice upon which he skates could wear very thin.
Tottenham sit three points away from West Ham in fourth, and with six of their last seven games after Sunday being against teams below them in the table, a first league double against the Red Devils since 1989 could reignite their dreams of a fourth placed finish and alleviate some of the pressure mounting on Mr Mourinho.
Last three Premier League meetings
Manchester United 1-6 Tottenham Hotspur (October 4, 2020)
In a spectacular Super Sunday, in which fierce rivals Liverpool slumped to a 7-2 defeat against Aston Villa in the late kick-off, Manchester United were embarrassed by Tottenham at Old Trafford as they fell to a 6-1 defeat, despite going in front.
The game remarkably saw three goals in its opening seven minutes, Bruno Fernandes gave the hosts the lead after just two minutes but Spurs impressively fought back, going ahead themselves through Son and Ndombele.
After a controversial sending off for Anthony Martial, Tottenham ran riot in Manchester, punishing the ten-man Red Devils for their defensive vulnerabilities, as another goal from Son and a Harry Kane strike made it 4-1 at half-time.
Rounding off a five star display, Serge Aurier added his name to the scoresheet and Kane converted a penalty in an illustrious display for Mourinho's side.
Tottenham Hotspur 1-1 Manchester United (June 19, 2020)
A late Bruno Fernandes penalty rescued a point for Manchester United, nullifying a bright start from Tottenham, in an intense encounter after the COVID-19 restart.
Spurs took the lead in the 27th minute through Dutch winger Steven Bergwijn - who's audacious low-drilled effort evaded David De Gea, with the Spanish goalkeeper being at fault having failed to deal with it properly.
Manchester United players were relieved - and no more so than David De Gea - when Eric Dier brought down Paul Pogba in the Tottenham penalty area, allowing Bruno Fernandes to do what he does best - converting a penalty with his trademark technique.
Manchester United 2-1 Tottenham Hotspur (December 4, 2019)
Mourinho fell to defeat on his first return to Old Trafford since his dismissal from the club - as a Marcus Rashford brace was enough to secure all three points for Solskjaer's side.
Rashford broke the deadlock after just six minutes, pouncing on a rebound from Davinson Sanchez to poke the ball past Paulo Gazzaniga before Dele Alli's brilliant equaliser in the 39th minute.
After a lengthy VAR check, Rashford was offered an opportunity to put his side in front after the video referee deemed Moussa Sissoko's challenge on the striker to have been a foul in the penalty area.
Rashford himself converted the penalty to earn a well-deserved victory for the Red Devils at Old Trafford.
Head to head in the Premier League
Tottenham wins: 10
Manchester United wins: 35
Tottenham scored: 56
Manchester United scored: 95
Manchester United's revival under Ole Gunnar Solskjaer
Despite a turbulent start to this Premier League season leaving a significant gulf between themselves and their inner-city rivals in addition to disappointing defeats in both domestic cup competitions, a golden opportunity has presented itself for Manchester United to end their season on a high.
The aftermath of the 6-1 drubbing in Manchester raised a number of questions on Solskjaer's capabilities, which were raised again after the Red Devils crashed out of Europe in emphatic fashion, but in the months that have followed there has been a notable turnaround at Old Trafford.
Firmly sitting in second position, Solskjaer's side are a dead cert to maintain Champions League football having embarked on an impressive unbeaten run of 11 games following their disappointing defeat against rock bottom Sheffield United, and it appears as if the confidence has been re-instilled at Old Trafford for the time being.
In addition, the Red Devils have impressively emerged as the bookies favourites for the Europa League, and unless another sensational exit from Europe repeats itself next week, their 2-0 lead over Granada should be enough to take them to the semi-finals of the competition.
Should Rashford and co. avenge the embarrassing defeat they suffered at the hands of their old boss earlier this season, a glorified end to a topsy-turvy season may begin to materialise in the red side of Manchester.
Score Prediction: Tottenham Hotspur 1-3 Manchester United
Goalscorers: Harry Kane, Bruno Fernandes, Marcus Rashford, Edinson Cavani
Following his strike against Granada in mid-week, Marcus Rashford took his Red Devils goal tally to 20 for the second successive season, meanwhile Harry Kane currently leads the Premier League golden boot race with 19 league goals to his name.
With two places undoubtedly saved for the strikers in England's Euro 2020 squad, Sky Bet are offering 7/1 odds for both English forwards to score in this fixture, as they both look to finish the season on a high.
Bruno Fernandes has 16 goals and 11 assists so far this season, with the Portuguese midfielder's exceptional return in the 2020/21 making him a likely contender for the Premier League Player of the Season - Fernandes opened the scoring in the reverse fixture between these two sides.
With both sides capable of potent counter attacks, dangerous set-piece plays and individual moments of greatness, this fixture is likely to produce a number of goalscoring opportunities.