The two clubs could end up facing each other in the Europa Conference League playoffs, but the hosts will still have ambitions of finishing higher.
Match preview
Despite the chances being slim, Twente still carry hopes of leapfrogging AZ Alkmaar into fourth place in the Eredivisie.
The Enschede-club currently lie fifth, six points behind AZ, but reaching fourth would absolutely assure them of a Europa Conference League spot, instead of them needing to go through the league's four-team playoff for the final place in Europe.
They will be hoping that the fact AZ have a semi-final double-header coming up in Europe will be a distraction for them, and allow them to close the gap.
However, with just three games to go, Twente will surely need to win all three to even have a remote chance, and facing Ajax on the final day looks a daunting prospect.
Ron Jans's side do enter the final sprint of the season in great form though, losing just one of their last eight games, picking up 15 points.
Nijmegen are much lower down the table with a far inferior points tally, but have just as good a chance of getting into Europe as their upcoming opponents.
With three of the four playoff spots for Europe already assured, there is a four-way battle for the final place.
Nijmegen, as well as Waalwijk, Heerenveen and Go Ahead Eagles are all separated by just four points going into the last three games, and only one of them will reach the playoffs.
This fixture represents a difficult challenge for NEC, but all of their rivals have tough games to come on paper too.
Rogier Meijer's men will be glad they are playing away from the Goffertstadion though given recent form, as they have lost three in a row at home, conceding 11.
It is a much different story on the road though, as NEC have taken 10 points from their previous five away matches, conceding only twice, against Ajax and Waalwijk.
There is a long way to go before they can start planning their trips around Europe, but it would be a fantastic achievement in just their second season back in the top flight.
Not since 2008 have Nijmegen competed in a European competition, and it would be just a fourth ever qualification in the club's history.
FC Twente Eredivisie form:
W
D
W
L
D
W
NEC Eredivisie form:
W
L
D
L
W
L
Team News
Dutch Under-21 international Anass Salah-Eddine was absent from the Twente squad last weekend in the win over Emmen, having spent the three previous games on the bench.
Max Bruns is their other injury absentee, as the 20-year-old has missed the last three matches with an ankle problem.
Nijmegen boss Meijer could be able to welcome back some members of his squad soon after extended periods out.
Calvin Verdonk is one important player who could return having not featured in almost three months, while goalkeeper Robin Roefs is also due to make a comeback soon.
However, Mathias de Wolf remains on the long-term absentee list with a muscle injury.
FC Twente possible starting lineup:
Unnerstall; Brenet, Pleguezuelo, Propper, Smal; Zerrouki, Vlap, Sadilek; Cerny, Ugalde, Misidjan
NEC possible starting lineup:
Cillessen; Van Rooij, Marquez, Sandler, El Karouani; Schone, Proper, Tannane; Tavsan, Dimata, Mattsson
We say: FC Twente 2-2 NEC
Twente have been strong at home and Nijmegen are tough to beat on the road, so there is little to separate the sides despite the gap in league position.