Arsenal's defeat at Stoke City last weekend, coupled with Manchester City's involvement in the League Cup final, saw Chelsea move four points clear and victory over Spurs would further galvanise their position.
Arsenal and City both have commitments in the FA Cup, while Liverpool, who stole into second place last weekend, do not have a fixture.
While City will have three games in hand by the time the weekend is out, Chelsea forward Andre Schurrle says that he and his team-mates are increasingly sure of their title credentials.
"We have to believe it. I think everyone believes it now. We have worked hard for this," said the Germany international, who scored a hat-trick in last weekend's 3-1 success at Fulham.
"We have to keep going, keep winning like we did at Fulham, then we will see at the end."
Jose Mourinho's Chelsea are unbeaten in 13 league matches, winning 10 and drawing three, but in Tottenham they face a team with designs on a UEFA Champions League place.
Tim Sherwood's side bounced back from a defeat at Norwich City by winning 1-0 at home to Cardiff City last Sunday and could close to within a point of the top four if they prevail at Stamford Bridge.
It is 23 years since a Spurs team won at Chelsea, but Sherwood believes that his side's status as underdogs could work in their favour.
"Games against Chelsea at the Bridge, Arsenal at the Emirates and Liverpool at Anfield, perhaps the pressure's off us a little bit and we can cause a surprise," said the Spurs manager.
"We're looking to mess up as many other people's seasons as we can, and enhance ours at the same time."
United's chance to rebound
Another team looking to capitalise on the inactivity of teams above them are Manchester United, who could draw level on points with sixth-place Everton if they win at West Bromwich Albion.
David Moyes's side have not played since slumping to a 2-0 loss at Olympiakos in the first leg of their UEFA Champions League last 16 tie on 25 February and begin the weekend 12 points below the top four.
United's last trip to The Hawthorns was for Alex Ferguson's final game as manager - a madcap 5-5 draw on the final day of last season - but while that sunny May day now seems a distant memory amid the club's current struggles, record signing Juan Mata says that there is plenty still to play for.
"A thrilling month is starting with five Premier League games against important rivals such as Liverpool and Manchester City," the Spanish midfielder wrote on his personal blog this week.
"We do know it is a crucial month to climb up positions on the league table and we are going to give our best to try and win every single match."
Saturday's truncated programme also features a potentially pivotal game at the foot of the table, with second-bottom Cardiff hosting bottom club Fulham.
The two teams are in danger of being cut adrift, having played at least a game more than the three teams immediately above them - Sunderland, West Brom and Crystal Palace - and defeat for either side could have costly consequences.
Elsewhere, Norwich host Stoke, while Southampton and their four England internationals - Adam Lallana, Jay Rodriguez, Rickie Lambert and mid-week debutant Luke Shaw - visit fifth-bottom Palace.