The Hoffenheim man was taken off with an unspecified problem in Friday's encounter with France, where a Kylian Mbappe brace consigned Ronald Koeman's men to a 2-1 defeat.
The Netherlands will no longer be able to finish in the top two if they are crushed by four or more goals on Monday, but Koeman has a ready-made replacement for Weghorst in Donyell Malen, who had a couple of bright moments after replacing the Burnley loanee.
A three-pronged attack would see Malen link arms with Bundesliga counterpart Xavi Simons, while Steven Bergwijn has thrown his hat into the ring with his assist for Quilindschy Hartman on Friday.
The Feyenoord left-back beat Mike Maignan at his near post for a debut goal, becoming the first defender to net on his Netherlands debut for 51 years since Dick Schneider did so against Peru in May 1972.
Hartman has surely done enough to keep Daley Blind at bay, while Denzel Dumfries will face stiffer competition on the right from Jeremie Frimpong but ought to hold his place regardless.
Another standout performer in the loss to France, Tijjani Reijnders should continue in midfield alongside Joey Veerman, with neither Marten de Roon nor Mats Wieffer laying down a marker in Amsterdam.
Goalkeeper Bart Verbruggen had a debut to forget on Friday, but the Brighton & Hove Albion man is set to continue behind a three-man wall of Nathan Ake, Virgil van Dijk and Lutsharel Geertruida.
Netherlands possible starting lineup: Verbruggen; Geertruida, Van Dijk, Ake; Dumfries, Reijnders, Veerman, Hartman; Simons, Malen, Bergwijn