Nuno Espirito Santo's side are on a four-match winless run, having not tasted victory since beating Chelsea on December 15th.
Palace are enjoying an inconsistent season, which was epitomised by the way they bounced back from heavy festive defeats to Liverpool and Aston Villa with a point against Leicester and a 2-0 win against Sheffield United.
When the two sides met in the Premier League in October, Wolves beat the Eagles 2-0 through goals from Rayan Ait-Nouri and Daniel Podence.
With both sides facing Premier League games a few days after the game, both Nuno and Roy Hodgson are expected to make numerous changes.
Wolves' well-documented injury troubles worsened with the news that Daniel Podence will miss numerous weeks instead of an expected return against Everton on Tuesday, while Marcal and Willy Boly will also miss the game.
Leander Dendoncker has returned to training after a four game absence, while Morgan Gibbs-White and Patrick Cutrone should feature having been recalled from their loans at Swansea City and Fiorentina respectively.
For Palace, Gary Cahill, Martin Kelly, Connor Wickham, Nathan Ferguson and former Wolves man Wayne Hennessey are out, while Christian Benteke will also likely miss the game having been withdrawn after 48 minutes against Sheffield United with a leg injury.
Wolves (4-2-3-1): Ruddy; Hoever, Coady, Kilman, Ait-Nouri; Perry, Otasowie; Corbeanu, Gibbs-White, Neto; Silva.
Crystal Palace (4-4-2): Butland; Ward, Dann, Sakho, van Aanholt; Townsend, McCarthy, Riedewald, Eze; Ayew, Batshuayi.
Ones to watch
With Wolves expected to make numerous changes, all eyes will be on the U23s who could make their first or second starts for the club.
Theo Corbeanu has scored four Premier League 2 goals this campaign, while Taylor Perry impressed in midfield against Aston Villa in the Carabao Cup last season.
For the Eagles, Eberechi Eze could cause Wolves' youthful backline problems if Hodgson starts the former QPR man.
Eze scored a stunning solo effort against Sheffield United last weekend and has earned plenty of plaudits since signing for Palace in August.
The sides last met at Molineux just over two-and-a-half months ago, when first-half goals from Rayan Ait-Nouri and Daniel Podence gave Nuno's side a 2-0 win.
Prior to losing their two visits to Molineux in 2020 the Eagles had a good record in WV1, having lost just one of their six visits between 2006 and 2019.
How to watch
The game kicks off at 7.45pm and is live on BT Sport Extra 2.