The Lilywhites have to put their past hoodoo of playing at the national stadium to one side, as they look to get one over the only team that finished above them in the table last season.
Forget a lack of transfers during the off-season - the biggest factor holding Tottenham back this coming campaign is playing their home fixtures around 13 miles West at a ground that they have notoriously struggled to perform at in the past.
One of the Lilywhites' more famous modern-day moments came at the 90,000-capacity venue in 2008 when beating Chelsea 2-1 in the EFL Cup final, but since then their record is close to atrocious, losing seven and winning just one of their last nine games there.
Boss Mauricio Pochettino was quick to play down suggestions that the success of Tottenham's season will come down to how successful they are in their new surroundings, but there will be plenty of focus on last term's second-placed side in this first home game.
A 2-0 victory over Newcastle United last weekend certainly helped lift the mood somewhat after being rocked by comments made by defender Danny Rose on the eve of the season - when essentially touting himself to rival clubs - having seen close friend Kyle Walker depart for Manchester City last month.
Yet while Spurs struggle to bring in new recruits, with Ajax defender Davinson Sanchez expected to become their first arrival at some point over the weekend, Walker remains the only first-team regular that they have lost during the summer, keeping their impressive core largely intact.
A couple of additions to bolster the bench may be all that it takes for Tottenham to continue their recent trend of improving their position season on season which, should that be the case, will see them crowned champions come next May.
There is no denying that their best-ever Prem finish last time out was built on a hugely impressive run of form at White Hart Lane, though, where they went the whole campaign unbeaten, winning 14 in a row to see things through.
Only once before have they won 15 home league games on the spin, with Southampton the last team to take points off Pochettino's men on home soil in May 2015, and Liverpool's all-time record of 21 will be in sight if they can end this worrying Wembley hoodoo.
Recent form in Premier League: W
For three months last season, after tweaking formation to go with Antonio Conte's favoured three at the back, Chelsea quite simply looked unstoppable as they brushed aside all comers.
Thirty-two goals were scored between October 1 and the end of the year, while four were shipped at the opposite end in a record-equalling 13-match winning run that essentially took them all the way to the title.
Notably, it was Tottenham who eventually ended the spectacular run of form on January 4 with an impressive team display, targeting Cesar Azpilicueta's side of the pitch to score a couple of identical goals in a 2-0 triumph at The Lane.
Chelsea recovered sufficiently to get over the line fairly comfortably, doing so with a couple of games to spare in the end despite the Lilywhites' best efforts, but they were never quite at their free-flowing best in the latter stages of the campaign even if the wins continued to steadily tick along.
There was a sense of opposition managers beginning to work them out, much like Pochettino did, leading to Conte experimenting slightly over the final final six league games - all ending in maximum points going the Blues' way.
All does not appear to be well at Stamford Bridge just now, however, having lost three competitive games in a row since lifting the title, beginning with back-to-back defeats to Arsenal in the FA Cup and Community Shield, before their shock loss to Burnley last weekend.
Perhaps the 3-2 setback will prove a blessing in disguise for Conte, who is seemingly desperate to bring in new recruits to add to a squad that already looks depleted at this early stage in proceedings, not helped by red cards shown to Cesc Fabregas and Gary Cahill last time out.
Not since 1973 have Chelsea lost their opening two games to a top-flight season, and it is 36 years since a defending champion kicked things off with successive defeats, but Conte will need no reminding that eight of his nine defeats in English football so far have come in the capital.
Recent form in Premier League: L
Recent form (all competitions): LL
Pochettino will be hoping to welcome Kieran Trippier back following the ankle problem he picked up in pre-season, ruling him out of the win over Newcastle and giving Kyle Walker-Peters a chance to impress - impress he did, too, being named sponsors' Man of the Match.
A three-man backline has worked well at times against Chelsea, including in their last league meeting, and that would likely allow Victor Wanyama to slot back into the middle of the park where he performed so well in 2016-17.
In terms of the visitors, Victor Moses could return at right wing-back after serving the ban carried over from the FA Cup final, but Cahill and Fabregas miss out due to the reds received against Burnley.
That has made a thin squad even thinner, though summer signing Tiemoue Bakayoko is closing in on a return to full fitness and Eden Hazard - back to his best last season - is also an outside contender to feature at Wembley.
Tottenham Hotspur possible starting lineup:
Lloris, Dier, Alderweireld, Vertonghen; Walker-Peters, Wanyama, Dembele, Davies; Alli, Eriksen; Kane
Chelsea possible starting lineup:
Courtois; Azpilicueta, Christensen, Rudiger; Moses, Kante, Luiz, Alonso; Willian, Hazard; Morata
Head To Head
Chelsea have lost just two of the last 17 meetings against Tottenham in league and cup, winning eight and drawing the other seven.
The most recent encounter between the two sides came at this venue in April, as the Blues edged out their rivals in a six-goal thriller to progress to the FA Cup final.
Spurs are unbeaten in 13 top-flight London derbies under Pochettino, however, winning nine of those over the past few years.
We say: Tottenham Hotspur 2-2 Chelsea
Just two weeks into the new Premier League season, Sunday's result in the English capital could have a huge bearing on who comes out on top come next May. Chelsea have already been written off by many neutrals, while Spurs themselves have to prove the doubters wrong, setting up an intriguing early-season contest under the famous arch.