Once pressing the "Lock" button in the top right of the Simulator, the device is locked, but the built-in SDK timers are still running.
If I have an enemy spawning every 1s, and I lock the game for 20s, unlocking the Simulator will add all 20 enemies that have been spawned during the lock at once. Attempting the same thing on my physical Playdate did not reveal the same issue. Timers are seemingly paused without any issue on real hardware.
I noticed that the real Playdate will also disconnect from the PC when locked, so I imagine the hardware enters a completely different state entirely, which is something that the Simulator isn't fit to do.