Spurs host the champions this weekend in a pivotal game that will have a huge bearing on their Champions League qualification fate.
Andre Villas-Boas has been stunned in recent weeks by the injury to Gareth Bale, and with a slump in results combined with their rivals picking up form, The Lilywhites have dropped out of the top four.
City do not have much to play for in the league since the title appears to almost certainly be heading to the other side of Manchester, and the probability of two sides usurping them and forcing them into fourth place and thus a Champions League playoff appear remote.
Roberto Mancini is a proud man who will want his side to finish strong and reduce the gap between themselves and United to a respectable amount to maintain some pride in the defence of their crown.
It should be a gripping game that will have a bearing on several sides in and around the European places. Here is all you need to know.
GARETH BALE UPDATE: Spurs are now confident that Bale will be able to face City this weekend. Andre Villas-Boas revealed "He's made good progress to train with the team so I think he'll definitely be up for selection" (via BBC).
Spurs will enter this game with two mindsets. On the one hand, their instincts will be that they need to win this game, having slipped outside of the top four, replaced by their rivals Arsenal and Chelsea.
On the other hand, Spurs might just remain calm in the knowledge that simply avoiding defeat could be good enough for the moment, as Arsenal still have to play United to play and Chelsea have to face the Champions elect too. Therefore, there are plenty more opportunities to gain points or see their rivals drop them.
Villas-Boas finds his side two points behind Arsenal with an inferior goal difference but possessing a game in hand. Spurs are a further point adrift of Chelsea in third, and they also have an inferior goal difference but no game in hand on the Blues.
The tactical mindset may be altered by how Arsenal fare against Fulham at Craven Cottage on Saturday. Should they drop points, Spurs may decide to set up in a more defensive manner, safe in the knowledge that they are unlikely to lose further ground on their ultimatum goal, fourth place.
Since Bale's explosion of form at the beginning of February, he has missed three games for Spurs, two through injury and one through suspension. In those games, Spurs have failed to pick up a victory, losing on aggregate 8-2.
If Bale is unable to play against City, it would represent a huge statement if Villas-Boas can manufacture a result of some substance to galvanise the rest of the group into believing that they are capable of earning a Champions League place without their star man.
Bale might, in fact, return to the Spurs lineup, but a decision on whether to risk the Welshman remains undecided.
Simply put, this game's importance depends on the mindset of the manager and whether the players can react to adversity in the short term. If results go the wrong way, Spurs could drop to sixth and be five points off a Champions League place by the end of the weekend.
Even with the kind run of fixtures that follow this game, that might be a mountain too steep to climb, hence avoiding defeat becomes almost paramount here for Spurs.
Manchester City will not be entering this game in as much of a relaxed fashion as some might believe.
Yes, in reality, there is only one more game that truly matters—the FA Cup final against Wigan.
However, the motivation and competitiveness will have risen organically amongst the group due to the possibility of several starting berths still to be decided for Wembley.
A burst of form from players such as Javi Garcia or Edin Dzeko might make Roberto Mancini think twice, while James Milner must maintain his form and prove he deserves to start even when David Silva returns.
Due to Samir Nasri's form and the task of Wigan, a side that Mancini will feel they can beat comfortably, Milner's work rate might not be needed. Milner could make way for Silva if he does not catch the eye over the coming weeks and Nasri's form continues as has done of late.
Moreover, Mancini will simply not allow this group of players to casually drop points over the coming weeks, even with a seven-point gap to third placed Chelsea.
The gap between them and United is 13 points and surely insurmountable, but such a wide margin of victory for United would be a major blow to the confidence of Mancini in his first defence of the title, casting doubt on his future in the process.
A strong finish in the league—reducing the gap to a single-digit margin—and victory in the cup final will probably be enough for him to keep his job for one more season, so the Italian manager will be determined to push his side right to the end.
Clint Dempsey is not the most orthodox of right wingers, but the American has been moved into this position since Gareth Bale's rise to prominence through the middle.
Even when the Welshman has been injured of late, Andre Villas-Boas has decided to maintain the former Fulham man out wide and use Lewis Holtby as the man tucked in behind Emanuel Adebayor.
Gael Clichy started confidently in the FA Cup semi-final against Chelsea last weekend, surging forward on a couple of occasions with penetrating runs that became the trigger for some of City's counter attacks that proved so effective against the Blues in the first half.
However, the Frenchman was soon pinned back and caught back tracking when Eden Hazard began to gain a little more confidence and seemed to struggle in the closing stages of the game as the Belgian made him decide whether to press hard or drop off and allow him time and space to run at the City defence.
I feel that Dempsey can do a similar job to an extent and will naturally drift into the middle in order to link with Adebayor.
If Dempsey can be cute enough with his runs, he will have plenty of joy finding space inside the penalty area that he will hope he can exploit with service from the likes of Kyle Walker's overlapping runs or Gylfi Sigurdsson's crosses cutting inside from the left flank.
It appears to be City's weak point right now, and if Walker can be brave enough to step forward and make a two-against-one matchup, it might be the key to Spurs' success.
Spurs predicted XI (4-2-3-1):
Hugo Lloris; Kyle Walker, Jan Verthongen, Michael Dawson, Benoit Assou-Ekotto; Moussa Dembele, Scott Parker; Clint Dempsey, Gareth Bale, Gylfi Sigurdsson; Emanuel Adebayor.
City predicted XI (4-2-2-2):
Joe Hart; Pablo Zabaleta, Vincent Kompany, Matija Nastasic, Gael Clichy; Gareth Barry, Yaya Toure; James Milner, Samir Nasri; Carlos Tevez, Sergio Aguero.