Las Blancas will be looking for another strong performance against their Dutch opponents after cruising to a 5-0 win on matchday three.
Match preview
Twente are competing in the group stage for the first time after getting the better of Cardiff City, Valur and Osijek in qualifying.
The Dutch side began the main draw with a successful outing against Celtic, with Kayleigh van Dooren scoring a brace in the home encounter.
Unfortunately for Twente, they have been unable to build upon that result, having fallen to back-to-back defeats against Chelsea and Real Madrid.
After losing 3-1 to the Women's Super League champions, Twente slumped to a heavy 7-0 loss in the Spanish capital, leaving them in third place and three points adrift of Las Blancas.
As a result, Twente will be eliminated with two games left to play if they lose to Real Madrid and Chelsea take something from their home meeting with Celtic.
Real Madrid are looking to make amends for last season's disappointing European campaign, which saw them finish bottom of their group with just a solitary point to their name.
Las Blancas have already picked up five more points in their current group-stage campaign, having won two and lost one of their three matches.
After losing 3-2 to Chelsea on matchday one, Real Madrid have gone on to claim two commanding home victories over Celtic and Twente.
They swept past Celtic via a 4-0 scoreline, before they eased to a 7-0 win over the Dutch champions thanks to a Maria Mendez brace as well as goals from Signe Bruun, Naomie Feller, Caroline Weir, Oihane Hernandez and Carla Camacho.
Unfortunately for Real Madrid, they came out the wrong side of a sizeable scoreline in Saturday's clash against rivals Barcelona, with Las Blancas shipping three first-half goals in a 4-0 defeat at the Estadio Alfredo Di Stefano.
Alberto Toril will be looking for a positive response on Wednesday, and his side will advance to the quarter-finals if they claim all three points and Celtic fail to beat Chelsea.
FC Twente Women Women's Champions League form:
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FC Twente Women form (all competitions):
Real Madrid Femenino Women's Champions League form:
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Real Madrid Femenino form (all competitions):
Team News
Wales international Olivia Clark will feature in goal for the hosts, with the shot-stopper set to be shielded by a back four of Leonie Vliek, Lieske Carleer, Anna Knol and Alieke Tuin.
At the opposite end of the pitch, Nikee Van Dijk is poised to lead the line against Real Madrid, with the striker likely to be flanked by Amanda Andradottir and Ella Peddemors.
As for the visitors, they are unable to call upon winger Athenea del Castillo, who is expected to be out until the new year after she recently underwent surgery on a fractured collarbone.
Brazilian full-back Antonia Silva is also set to miss Wednesday's fixture after being forced to sit out the last two matches with an injury issue.
Linda Caicedo and Bruun dropped out of the lineup for Saturday's defeat against Barcelona, but the pair could be brought back into the side for the trip to the Netherlands.
FC Twente Women possible starting lineup:
Clark; Vliek, Carleer, Knol, Tuin; Te Brake, Van Ginkel, Van Dooren; Andradottir, Peddemors, Van Dijk
Real Madrid Femenino possible starting lineup:
Misa; Hernandez, Mendez, Lakrar, Carmona; Leupolz, Angeldal; Feller, Weir, Caicedo; Bruun