Vitesse are without a victory in six league games, while Twente are unbeaten in eight, so it is no surprise that Ron Jans's side lead the Arnhem outfit by 19 points in the standings.
Match preview
After suffering a 4-0 thrashing at the hands of Sparta Rotterdam, Vitesse ended November with back-to-back draws, meaning they entered the World Cup break on a three-match winless run.
Phillip Cocu would have been desperate for his players to hit the ground running after the break, but they have picked up where they left off before the World Cup, heightening relegation fears at the GelreDome.
Earlier this month, Vitesse returned to action with draws against AZ Alkmaar and NEC before suffering a 1-0 defeat to PSV Eindhoven, despite giving a decent account of themselves against the title contenders last time out.
Cocu's side have now lost eight of their 17 Eredivisie outings this season, picking up three wins and six draws along the way, and they find themselves just three points clear of the automatic relegation places as a result.
Having managed to win only one of their eight home league games this term - conceding 19 goals in the process - Vitesse are in real danger of dropping into the second tier for the first time in over three decades.
At the opposite end of the table, FC Twente find themselves fourth - four points behind first-placed Feyenoord - having lost just three of their 17 league encounters this season.
The Pride of the East enjoyed a five-game unbeaten run in the Eredivisie before the World Cup, chalking up three wins and two draws, and they have extended that run to eight games since the break, adding two victories and one draw to their tally.
After beating FC Emmen 2-0 in their first game back, Twente held Ajax to a goalless draw in Amsterdam before securing a 2-0 victory over FC Utrecht, dominating Michael Silberbauer's side last time out.
Twente have built their league campaign on a remarkable defensive record, conceding just nine goals, and they have also achieved 10 clean sheets, meaning they have managed to keep a clean sheet in almost 60% of their Eredivisie encounters this term.
Having taken 18 points from a possible 24 since their last defeat, which came against Feyenoord back in October, Jans's men will be confident of heaping more misery on struggling Vitesse.
Vitesse Eredivisie form:
L
D
D
D
D
L
FC Twente Eredivisie form:
W
D
D
W
D
W
Team News
Vitesse will be without suspended goalkeeper Kjell Scherpen on Wednesday after the Brighton & Hove Albion loanee picked up a red card last time out.
Having made seven Eredivisie appearances this season, Daan Reiziger is expected to replace Scherpen in the starting XI, although Cocu may decide to place Jeroen Houwen between the sticks.
Former PSV defender Nicolas Isimat-Mirin could make his debut for Vitesse on Wednesday, but the usual centre-back pairing of Enzo Cornelisse and Ryan Flamingo should start the game.
As for FC Twente, club captain Wout Brama has not featured since September following ankle surgery, while fellow midfielder Michal Sadilek continues to recover from a groin injury.
Ricky van Wolfswinkel and Virgil Misidjan have both bagged six goals and five assists across all competitions this season, so they will start alongside Vaclav Cerny in attack.
Vitesse possible starting lineup:
Reiziger; Arcus, Flamingo, Cornelisse, Dijks; Tronstad, Meulensteen; Manhoef, Bero, Wittek; Sankoh
FC Twente possible starting lineup:
Unnerstall; Brenet, Hilgers, Propper, Smal; Zerrouki, Vlap, Kjolo; Cerney; Van Wolfswinkel, Misidjan
We say: Vitesse 0-1 FC Twente
When you couple the contrasting form of these two sides with FC Twente's phenomenal defensive record, all the signs point towards another clean-sheet victory for the Pride of the East.