The Gunners travel to West Bromwich Albion in the under-21 league, with Wilshere among those in the squad.
The England international is expected to start the game and play an hour in his first outing for 14 months.
The 20-year-old missed the whole of last year after hobbling off in a pre-season match against the New York Red Bulls in the Emirates Cup and has suffered multiple set-backs since.
Speaking last week, manager Arsene Wenger said: "He will play on Monday. He will play his first game with the under-21s, maybe an hour or something like that.
"It's another important step but he has not played for 14 months so we have to calm your impatience a little bit.
"It is fantastic for him. When you are at that age and are out for such a long time, it is absolutely massive to take [for] him and Frimpong. It is massive for them to come back and for us as well."
Wenger also ruled out the possibility of Wilshere playing for England against San Marino or Poland later this month.