Mauricio Pochettino's side may have come up short at Wembley, but they remain just four points adrift of the Premier League leaders and will be determined to rebuild momentum at Selhurst Park.
Spurs are the division's in-form team, having won seven consecutive top-flight fixtures in recent weeks, but will encounter an Eagles side brimming with confidence.
Sam Allardyce's men climbed seven points clear of the relegation zone with victory over Liverpool on Sunday and need just one more win to secure their survival.
Victory over their north London rivals on home turf would be a fitting way to achieve such a goal.
Scroll down for Standard Sport's comprehensive preview of the big match....
Crystal Palace host Tottenham at Selhurst Park with kick-off scheduled for 8pm on Wednesday, April 26.
TV AND LIVE ONLINE COVERAGE
The match will be televised live on Sky Sports 1, with coverage starting from 7:30pm.
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Allardyce could be excused for opting not to alter a winning formula after seeing his side secure a crucial victory at Liverpool on Sunday.
But the 62-year-old has hinted he will make widespread changes in order to keep his key players fresh for the run-in.
Such an approach could see both Christian Benteke and Wilfried Zaha drop to the bench, with Jeffrey Schlupp and Fraizer Campbell pushing for starting berths.
Mamadou Sakho will come back into the side after being ineligible for the trip to Merseyside while left back Patrick van Aanholt is expected to make his first start since early March.
Pochettino could opt to make a couple of changes, having seen his Heung-min Son experiment fail at Wembley.
The Argentine coach's selection will revolve around what system he chooses to adopt, with a three-man defence the most likely option.
Ben Davies is expected to come back into the team at left wing back while Kyle Walker will be hopeful he has done enough to usurp Kieran Trippier.
Victor Wanyama and Mousa Dembele's midfield partnership should give the visitors combination of mettle and nous needed to cope with a tricky Palace attack.
Newly crowned PFA Young Player of the Year Dele Alli will be aiming to make an impact at the ground where he scored a sensational volley last season.
Crystal Palace starting XI: Hennessey; Ward, Delaney, Sakho, Patrick van Aanholt; Milivojevic, McArthur; Townsend, Puncheon, Schlupp; Campbell
Tottenham starting XI: Lloris; Dier, Alderweireld, Vertonghen; Walker, Wanyama, Dembele, Davies; Eriksen, Alli; Kane
BETTING ODDS (via 888 Sport)
- Palace to win: 9/2
- Spurs to win: 3/5
- Draw: 16/5
Click here to place a bet. Odds correct as of April 24 at 2pm.