After using an application on the 2. Monitor i can not activate MSFS on the main monitor with a left mouse click nor can i switch to a windowed MSFS with Alt + Enter. MSFS has to be stopped using the taskmanager.
Check your screen settings in videocard control center and see if screen setup changed.
If changed try to set all to 1 screen and add the other one later.
If not changed you can try the next option
In usercfg.opt
There are lines fullscreen = 1
And windowed mode = 0
Change this to fullscreen = 0
And windowed mode = 1
Now the sim should start in windowed mode
If use after this in the sim alt + enter you switch to fullscreen and when leave the sim itt should be saved in usercfg.opt like before