Last season's edition of the fixture all but ended Tottenham's hopes of winning the Premier League title, and the North Londoners will be after revenge against their struggling hosts this weekend.
The pressure on the shoulders of West Ham boss Slaven Bilic has eased with a couple of improved results recently, but the spotlight is still on the Croatian.
Reports claimed that he had just one match to save his job following three consecutive defeats to open up the new Premier League season, but West Ham now head into this weekend having lost just one of their last five outings across all competitions.
A 2-0 win over Huddersfield Town earlier this month handed the Hammers their first points of the season, and they added one more to their tally during a dour goalless draw with West Bromwich Albion last weekend.
An EFL Cup win over Bolton Wanderers has stretched their unbeaten run to three games - keeping clean sheets in each - but the visit of Spurs represents a major step up in quality and West Ham's position is still fragile enough that defeat could send them back into the relegation zone.
The Hammers' improved form has coincided with the return of Andy Carroll and subsequent switch to a 3-4-3 formation which has also seen Bilic change his style of play - his side have averaged more than twice as many crosses during the last two league games as they did during their opening three.
An aerial bombardment may be coming the way of Spurs, then, as West Ham go in search of back-to-back league wins at the London Stadium for only the second time. Across all competitions this term Bilic's side have won both outings in front of their own fans, scoring five goals without reply in the process.
West Ham have not won their opening two home league games in a season since 2012-13, but they do tend to up their game against Spurs, winning this exact fixture in both of the past two seasons, each by a 1-0 scoreline.
Indeed, Bilic has won all three of his home managerial meetings with Mauricio Pochettino by a single goal to nil, including two with West Ham and one while in charge of Besiktas in the 2014-15 Europa League group stage.
Recent Premier League form: LLLWD
Recent form (all competitions): LWLWDW
Tottenham away games may be silently relished by Pochettino and his players at the moment, with talk of the Wembley curse subsiding during the buildup to a match on the road.
More dropped points at their temporary home during a 0-0 draw with Swansea City last weekend leaves them now five points adrift of the leading Manchester clubs, and that is a gap they cannot allow to grow much bigger.
Away trips to West Ham have not provided much more joy in recent seasons, though, and even at this early stage of the campaign defeat in East London could have a significant impact on their title hopes - as it has in both of the past two seasons.
Tottenham's away form has been good of late, though. Pochettino's side have won both of their league outings on the road so far this season without conceding a goal - including an impressive 3-0 win over Everton in their most recent away game.
Indeed, including the tail end of last season Spurs have scored 18 goals and conceded just twice in a four-match winning streak on the road, with their goal difference of +16 in that time being the top flight's best over a four-game away spell since 1892.
Another victory on Saturday would see them equal their club record of five consecutive Premier League away wins, while also lifting them into third place for a few hours at least.
Spurs are also unbeaten in their last nine league outings in September - a record no doubt helped by Harry Kane's penchant for following up a barren August with a fruitful spell in front of goal.
The England international may have drawn a blank against Swansea last time out, but he has scored six goals already this month for club and country and in 2017 has 23 goals in just 22 league games - only Lionel Messi, Edinson Cavani and Robert Lewandowski have more in Europe's top five leagues.
Should Kane be on form again this weekend then Spurs will be confident of opening the season with three consecutive away wins for the first time since 1991-92, although they have lost their last two London derbies and could lose three in a row for the first time since August 2005.
Recent Premier League form: WLDWD
Recent form (all competitions): LDWWDW
Pochettino is expected to welcome a host of first-team players back into the side after taking the opportunity to rest them during the EFL Cup win over Barnsley in midweek.
Among those in line to return is Ben Davies, who also sat out last weekend's match against Swansea due to an ankle injury.
Kane is expected to lead the line once again having scored nine goals in his last four Premier League away games, five goals in five games against West Ham and 19 in 28 Premier League London derbies.
The Hammers will be without their own capital specialist as Manuel Lanzini, who has scored nine of his 14 Premier League goals in London derbies including three in his last four meetings with Spurs, misses out with a knee problem.
The hosts are also missing Pedro Obiang and James Collins through injury, while the likes of Marko Arnautovic and Andre Ayew may once again be forced to settle for a place on the bench despite featuring in midweek.
West Ham possible starting lineup:
Hart; Fonte, Reid, Ogbonna; Zabaleta, Kouyate, Noble, Cresswell; Antonio, Carroll, Hernandez
Tottenham possible starting lineup:
Lloris; Alderweireld, Sanchez, Vertonghen; Trippier, Dembele, Dier, Davies; Eriksen, Alli, Kane
Head To Head
West Ham have won three of their last four home meetings with Spurs, including in both of the past two seasons, keeping a clean sheet in each victory. Another win this weekend would see them string together a run of three consecutive home victories over Spurs for only the second time in the Premier League - and the first since a four-game streak from 1997 to 1999.
Indeed, the Hammers have beaten their fiercest Premier League rivals 14 times in the Premier League era, which is their highest win tally against any team in the competition.
Lanzini's goal in the corresponding fixture in May was effectively the killer blow to Tottenham's title hopes, while the reverse fixture saw Kane score two late goals as Spurs twice came from behind to win 3-2 at White Hart Lane.
We say: West Ham 1-2 Tottenham
West Ham have not been particularly impressive this season, and they are coming up against a team who have been scoring for fun on the road in recent Premier League games. The Hammers are sure to put up a fight against their biggest rivals in the division, but we're backing the visitors to come out with all three points.