The Spaniard was declared unfit to ride in the eighth round of the season on Sunday morning due to a rib fracture sustained over the course of a bruising German Grand Prix last weekend.
Marquez crashed five times across the Sachsenring round, with his final fall in warm-up leading to a small hand fracture and ruling him out of the main grand prix.
Further check-ups revealed an ankle injury and a rib fracture, with the latter now forcing him to skip the final race before the summer break.
Marquez’s absence will leave Iker Lecuona - replacing an injured Joan Mir - as the factory Honda team’s sole representative at Assen, a track it last won at in 2018.
“Marc Marquez will sit out the Grand Prix at the TT Circuit Assen after being declared unfit as a result of the injuries sustained at the German GP last week, which have been aggravated further in Assen,” read a short statement from HRC.
Marquez was planning to take part in the Dutch GP to gather as much data as possible for his Honda engineers to improve its troubled RC213V.
He endured a troubled sprint race en route to 17th on Saturday, as he took a safety-first approach at Assen.
Speaking afterwards, the six-time MotoGP champion said he is going through the “worst moment” of his professional career, not counting for his injuries.
"Apart from the [2020] injuries, this is the worst moment of my sporting career," he said.
"But defeat is the easy option. And I will never choose the easy way.
"Right now I'm riding for myself; for my engineers. Going half a second a lap slower, the problems are the same."
Marquez has so far competed in three actual grands prix this year, all of which ended in retirement.
He did qualify on pole position for the season-opening Portuguese GP, but a crash with Miguel Olivera in the race left him with a fracture that required surgery, forcing him out of the following three rounds.
Marquez’s troubles have left Repsol Honda last in the teams’ standings, while Honda is only ahead of Yamaha in the constructors’ championship - largely thanks to LCR rider Alex Rins’ victory in the Americas GP.