A tally of 53 points from 34 games saw the hosts finish sixth in the just-concluded Eredivisie season, three points and one spot above the visitors.
Utrecht signed off their league campaign with a six-game unbeaten run following 1-1 draw against PSV Eindhoven on Sunday.
Rene Hake's men went into the break with a one-goal lead which was given to them by Sander van de Streek, but that advantage was wiped out barely five minutes into the second half courtesy of Marco van Ginkel's first goal in three years.
The Domstedelingen are now set for a crunch clash against a side who they failed to beat in any of the two league meetings last term.
However, Wednesday's hosts have only lost one of their previous nine home games against the visitors which came back in 2016.
Groningen were on the receiving end of a 1-0 defeat in their season finale against PEC Zwolle at the MAC³PARK Stadion on Sunday.
The contest was level heading into the final 10 minutes before Ko Itakura inadvertently put the ball into his own goal.
Trots van het Noorden missed out on an opportunity to move level on points with Utrecht as a result of that stalemate.
Danny Buijs's men have not featured in any European tournament since 2016, and a huge step in ending that run awaits them on Wednesday.
Wessel Dammers missed Groningen's final three games with a muscle injury, and the 26-year-old is a major doubt for Wednesday's clash.
The visitors could also be without the services of Gabriel Gudmundsson who has not featured since April due to a knock.
Utrecht's Reda Akmum is unavailable for the game as he remains sidelined with a damaged knee which has kept him out of action for the past three months.
Christopher Mamengi has missed a huge chunk of the campaign through an ankle injury which he picked up while on duty with the reserve team.
FC Utrecht possible starting lineup:
Oelschlagel; Warmerdam, Janssen, St .Jago, Ter Avest; Van Overeem, Van de Streek, Emanuelson; Boussaid, Kerk, Gustafson
Groningen possible starting lineup:
Padt; Van Hintum, Itakura, Te Wierik, Dankerlui; Schreck, Van Kaam; Suslov, El Hankouri, Da Cruz; Strand Larsen
We say: FC Utrecht 2-1 Groningen
There was little to choose from between the teams over the course of the last campaign, and we are expecting a tight affair in this one. We are also backing the hosts to claim a narrow victory over the visitors.
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