I have a very similar setup to you and experience the same problems after the main screen goes into sleep mode. My main screen is set to 200% scaling, screen 2 is set to 100% (normal) and screen 3 is set to 150% scaling. This might cause Nuendo some problems.
In addition to losing the correct placing of everything as per the current workspace, the Transport Panel often becomes very small and can not be placed where it should be (at the bottom of the main screen (for me)). Also, the dropdown menus on the top menu bar (File, Edit etc.) either become very small, appear in the wrong places or disappear completely. Very frustrating.
One thing that I’ve tried today that appears to help the situation is to turn off the main screen’s auto-sleep mode. My screen was set to go off after 40 minutes. If I then need to leave the screen for some time I ‘minimise’ the main screen which has the benefit of minimising all three screens.