Ronald Koeman's squad are also set to be faced by France and Austria in a testing Group D quartet, so they must push aside some recent injury woes and get off to a fast start this weekend.
Leaving a substantial hole in midfield, Barcelona star Frenkie de Jong has failed to recover from an ankle problem, while Atalanta BC's Marten de Roon and Teun Koopmeiners are also unavailable due to injury.
Therefore, candidates such as Tijjani Reijnders, Ryan Gravenberch, Jerdy Schouten and PSV playmaker Joey Veerman will all vie for selection in the Oranje's engine room.
Once a defender of great renown, Koeman has far fewer problems at the back, where captain Virgil van Dijk - who scored in two recent friendly wins - is leader of a defensive line with substantial pedigree.
Two more Premier League players, Nathan Ake and Micky van de Ven, are battling with Daley Blind to start at left-back; Stefan de Vrij or Matthijs de Ligt could partner Van Dijk in the centre; while there are plenty of options on the right.
Denzel Dumfries, who set up several goals in qualifying, must see off competition from Jeremie Frimpong and Feyenoord's Lutsharel Geertruida, though Frimpong could alternatively feature further foward.
In attack, Memphis Depay is expected to lead the line this weekend, as Brian Brobbey has been struggling with a hamstring issue; Wout Weghorst and late call-up Joshua Zirkzee are back-up options more likely to be introduced from the bench.
Meanwhile, Brighton & Hove Albion goalkeeper Bart Verbruggen seems to have won his tussle with Mark Flekken and Justin Bijlow to start between the posts.
Netherlands possible starting lineup: Verbruggen; Dumfries, Van Dijk, Ake, Van de Ven; Schouten, Veerman; Simons, Reijnders, Gakpo; Depay