Five players from each team are on the court during an NBA 2K game, mirroring regulation basketball. That means a standard five-on-five matchup has 10 active players on the playing surface at once, excluding substitutes on the bench.
The five-player structure dates back to the development of basketball in the late 19th century. James Naismith invented the sport in 1891, and teams of five became standard by the late 1890s. The lineup traditionally contains a point guard, shooting guard, small forward, power forward, and center, although modern basketball often uses flexible or positionless roles.
Substitutions do not change the on-court limit. Coaches can replace players when the rules allow, but each team must still have no more than five active players playing at a time. NBA 2K also includes formats such as three-on-three and other specialized modes, so the answer applies to a normal NBA-style game rather than every possible mode or basketball variation.