With what he calls their best team since 2001, manager Harry Redknapp says Spurs chance to end United's 11-year spell may be at hand.
Tottenham are 'best equipped to win' now against Manchester United
Redknapp's men welcome United to north London knowing victory will reduce the gap between them and the champions to just five points with 11 games of the season remaining.
The omens do not look good for Redknapp's team, however.
Redknapp, thought, is confident going into the game, saying: "It is the best equipped team to win since 2001.
"It will be difficult. Manchester United are still a great team, so you know what you are in for.
"We will have to be at our very best if we are going to get a result from the game but we have a good chance."
Paul Scholes and Ryan Giggs were on the pitch the last time United lost to Spurs, who were then managed by Glenn Hoddle.
"It's fantastic to see them playing," Redknapp said.
"They are just amazing players and they are a great credit to their profession."
Redknapp's team are now facing two weeks that could either make or break their season.
Having cruised past the majority of their opponents while Chelsea and Arsenal have been struggling, Spurs now find themselves just four points in front of their London rivals ahead of Sunday's game, which is followed by away trips to Everton and Chelsea.
They have been boosted by the gradual return to fitness of Rafael van der Vaart, who looks set to start, while Ledley King and Kyle Walker should also be fit.
One man they will be without is influential midfielder Scott Parker after his sending off against Arsenal last weekend.
Either Brazil international Sandro or rising star Jake Livermore, will replace him.
Despite their fine record against Spurs, Michael Carrick, the United midfielder, knows today will be a significant test.
"Over the years there have been some classic games between the two teams," said the former Tottenham player, 30.
"We have a decent record down there, although it won't count for much this weekend.
"Losing at Arsenal was a big blow to them, but they will be looking to get back on track."
With rivals Manchester City setting the pace at the top of the table, Carrick is inclined to agree with midfield partner Scholes, who said United may have to win every game to be certain of coming out on top.
"We might have to win them all," admitted Carrick.
"But we feel confident because we have not lost many games all season.
"At this point you need to try to win every game anyway because this is where it starts getting serious. Wins and draws can make a huge difference.
"When Ryan Giggs scored at Norwich last week you saw how we responded and what it meant to everyone."
Yohan Cabaye may be in his first season in England, but the importance of the Tyne-Wear derby was made clear to him on the day he signed for Newcastle.
The France international, 26, said: “When I signed [from Lille], someone told me straight away about Sunderland, and said, ‘There are only two games in the season you can’t lose: Sunderland away and Sunderland at home’.”
Sunderland lost 4-0 at West Bromwich Albion in their last league game but previously they were on a run of 15 games which yielded just three defeats.
Wolves began interim manager Terry Connor’s reign with a 2-2 draw at Newcastle United last weekend.
Former captain Henry said: “The players have been here a long time and appreciate everything Mick has done but we have got a job to do. We are professionals and the day Mick was sacked we got together and said, whoever comes in, we have got to embrace the way he does things and his philosophy.”
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