Manchester United, which leads City by 13 points, can clinch its 20th English title with a victory at home to Aston Villa on Monday if City loses at White Hart Lane.
City has saved some of its best form for the latter stages of the season, winning six of its last seven league matches, but the team will not be as fresh as Tottenham, which has been on a 10-day break since being knocked out of the Europa League quarterfinals.
Physical edge may not be the only factor as Tottenham striker Emmanuel Adebayor, who used to play for City, predicted that his opponents will start fighting each other on the field if things don't go their way.
"If we put them under pressure we have a chance to win for sure," said Adebayor, who clashed with coach Roberto Mancini when he played for City and was made to play with the youth team.
"I was there and whenever things are not going their way there will definitely be a fight or an argument on the pitch and that is how we can take them down."
Tottenham has not won a game this calendar year in which winger Gareth Bale has not scored and head coach Andre Villas-Boas will be hoping his star player recovers from an ankle injury in time for Sunday's match.
A City win would also put a huge dent in Tottenham's Champions League ambitions with the North London club currently two points behind fourth-place Arsenal, having played one game less, and three points behind Chelsea in third.
Chelsea interim manager Rafa Benitez returns to the club he led to the 2005 Champions League title on Sunday as the Blues travel to Liverpool hoping to consolidate their strong position in the race for the league's top four.
A grueling fixture list could hamper Chelsea's chances as it tries to maintain a challenge on two fronts in the Premier League and the Europa League, where it has reached the semifinals.
After Liverpool, Benitez's team still has to face Manchester United, Tottenham and Everton, as well as relegation-threatened Aston Villa.
"We're obviously in the semifinals of the Europa League but realistically we want to be playing Champions League football, that's what it's about for this football club," said captain John Terry, who scored two goals in a 3-0 win over Fulham on Wednesday.
"It's a busy schedule because we play on a Thursday (in the Europa League) and I think we have about four games in 10 days or something like that, but we've got the squad, the manager's rotating and everybody's playing a part."
Liverpool manager Brendan Rodgers will also be a familiar face to his opponent on Sunday after previously coaching Chelsea's reserve and youth sides.
Ten points adrift of fourth place, the Reds' hopes of qualifying for the Champions League appear to be over, but Liverpool will be motivated by closing the gap on local rival Everton, which is currently six points ahead in sixth.
Everton travels to relegation-threatened Sunderland on the back of a goalless draw against Arsenal, which faces a trip Fulham.
"We've got to start turning these draws into wins if we are going to keep potentially challenging for the top four," Everton defender Phil Jagielka said. "Saturday is going to be a very important game and I'm sure the manager is looking forward to that now. Hopefully we can keep another clean sheet and score a goal or two."
At the bottom, Queens Park Rangers and Reading can be relegated if they lose to Stoke and Norwich, respectively, and other results go against them. Wigan, which currently occupies the last relegation spot, faces West Ham.
Mid-table teams Southampton and Newcastle will be looking to extend their advantage over the bottom clubs as they travel to Swansea and West Bromwich Albion, respectively.