Roy Hodgson's men have been in woeful form of late and have just four points to their name, but Spurs are a scalp to be claimed, and the Eagles have already dug their talons into Chelsea this season.
Mauricio Pochettino is likely to rotate his team after their heroic 3-1 win over Real on Wednesday, but he will expect all three points as Spurs look to get back to winning ways in the Premier League after losing to Manchester United last weekend.
Toby Alderweireld limped out of Spurs' win over Real with a hamstring injury, and Pochettino admitted afterwards that it will be "difficult" for the Belgium international to play against Palace.
Hugo Lloris and Ben Davies also picked up knocks, but the pair completed the 90 minutes and are likely to be fit, though the Welshman may be rotated, with Danny Rose waiting in the wings.
Victor Wanyama is a long-term absentee, but Erik Lamela has returned to first-team training and is in contention to be named in the matchday squad.
Neither side has any suspensions to worry about heading into the match.
SPURS POTENTIAL STARTING LINE-UP
With Spurs competing on multiple fronts, rotation can be expected against Palace, though in central defence options are limited, and Eric Dier is likely to play at centre-back in place of the injured Alderweireld. He will likely be supported in a back three by Davinson Sanchez and Jan Vertonghen, who were both excellent against Real Madrid.
Pochettino enjoys rotating his full-backs, and thus Serge Aurier and Danny Rose may replace Kieran Trippier and Ben Davies, respectively.
Mousa Dembele made a cameo appearance for Spurs from the bench, and may start ahead of the impressive Harry Winks, allowing the Englishman a rest, while Son Heung-Min may return to the starting XI in an attacking role.
Harry Kane overcame fitness concerns to play and impress against Real, and he should lead the line, with Christian Eriksen and Dele Alli, scorer of two goals on his return to the Champions League, in support.
CRYSTAL PALACE TEAM NEWS
Palace have a number of problems heading into the game, not least the fact that they have picked up just four points thus far this season and lie bottom of the Premier League table.
Patrick van Aanholt is a major doubt with a hamstring injury, while midfielder Lee Chung-Yong has a muscle problem. James McArthur and Mamadou Sakho could be in contention if they can overcome an ankle injury and a calf strain, respectively.
Strikers Christian Benteke and Connor Wickham are both long-term absentees.
OPTA MATCH FACTS
Spurs have won each of their last four Premier League games against Palace, conceding just once, since losing 2-1 in January 2015 at Selhurst Park.
Palace have failed to score in any of their last four away league matches at Spurs since a 1-1 draw in December 2004 (D1 L3); their only Premier League win at Spurs came in November 1997, winning 1-0 courtesy of a Neil Shipperly goal.
In four home Premier League games against Crystal Palace, Mauricio Pochettino is yet to see his sides concede a goal (one match with Southampton, three with Spurs).
Harry Kane has missed nine Premier League games for Spurs since the start of 2016-17 - in those games, Dele Alli and Son Heung-Min have both scored four goals.
Tottenham have lost both of their London derbies in all competitions at Wembley this season, as many as they'd lost in their last 16 at White Hart Lane under Mauricio Pochettino (W10 D4).
TV COVERAGE & KICK-OFF TIME
The match, which kicks off at 12:00 in England will not be shown on live television in the UK. Highlights will be broadcast on Match of the Day 2 at 22:30 on BBC One