While the Cottagers make the short trip to the London Stadium in 13th position, they sit just nine points adrift of their hosts.
Match preview
Had West Ham left Bayer Leverkusen with a goalless draw on Thursday night, David Moyes would have been receiving credit for nullifying one of the season's most impressive teams.
Instead, an end result of a 2-0 defeat without laying a glove on the Bundesliga outfit has led to criticism of the Scot's tactics in Germany, West Ham now with just two wins from eight matches in all competitions.
Overturning such a deficit against a team that have not lost a single match all season is highly unlikely, and it could lead to Moyes paying more attention to the Premier League.
Last weekend, West Ham ended a run of four matches without success in the top flight as they posted a 2-1 victory away at Wolverhampton Wanderers, overturning a half-time deficit to prevail at Molineux.
With Manchester United again dropping points, the Hammers are within one point of sixth, yet the greater concern will lie with the chasing pack who have played fewer matches than West Ham.
In December's reverse fixture at Craven Cottage, West Ham lost 5-0 having delivered one of their worst performances of the season, yet it will be Marco Silva who may be worried about conceding so many goals in this game.
Fulham have shipped three goals in each of their last two away fixtures at Sheffield United and Nottingham Forest, extending their dismal away record.
Just two wins and and 11 points have been registered from 16 matches, while Fulham are also on a three-match run without a victory courtesy of last weekend's 1-0 loss at home to Newcastle United.
With the possibility of reducing the gap to West Ham to six points with five matches left, Fulham are not out of European contention just yet, but they will need to show the level of display that they produced in seeing off Manchester United at Old Trafford in February to keep on track.
That said, Fulham have suffered defeat on their last five visits to West Ham, a run stretching back to 2010.
West Ham United Premier League form:
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D
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W
West Ham United form (all competitions):
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Fulham Premier League form:
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L
Team News
With Edson Alvarez available again after serving a European suspension, Moyes could revert back to a defensive four.
Michail Antonio is expected to remain down the centre of the attack in place of Jarrod Bowen, who Moyes does not expect to return for this contest due to a rib injury.
Goalkeeper Alphonse Areola and midfielder Kalvin Phillips should also miss out through injury, while Ben Johnson, Nayef Aguerd and Max Cornet are all options if Moyes wishes to introduce fresh legs.
Silva has a fully-fit Fulham squad at his disposal and that could lead to alterations after the defeat to Newcastle.
Adama Traore may finally be handed his first Premier League start of the campaign, while Sasa Lukic and Harry Wilson are also in contention.
Providing that Rodrigo Muniz is passed fit after a recent issue, Raul Jimenez will have to make do with a spot among the replacements.
West Ham United possible starting lineup:
Fabianski; Coufal, Mavropanos, Zouma, Emerson; Alvarez, Soucek; Kudus, Ward-Prowse, Paqueta; Antonio
Fulham possible starting lineup:
Leno; Castagne, Adarabioyo, Bassey, Robinson; Palhinha, Cairney; Iwobi, Pereira, Willian; Muniz
We say: West Ham United 2-2 Fulham
Given the inconsistency of both sides, this is a difficult match to predict. Moyes must also find a balance with the second leg with Leverkusen to come, and it could lead to a slightly chaotic - but entertaining - share of the spoils being played out.