Hello @Mendler,
Let me first of all say you shouldn’t be experiencing significant performance impact in ZBrush solely from running your monitor at its native resolution. If you’re experiencing performance slowdowns, it’s probably coming from a different source, and you may want to contact Pixologic Support.
You may start to see performance impact from increasing the resolution of your canvas. If your document size is set to a higher resolution, you may start to see performance become somewhat slower than working on a document of a smaller size.
This is a tricky question because of the OS’s high DPI scaling involved with high resolution displays. Most existing content is not comfortable to view on high resolution displays without some sort of magnification. To answer your question, no, ZBrush cannot run at a different resolution than your display is set to, but it can run without high DPI scaling.
If you’re using a high resolution display, your OS is probably scaling the program window larger to some degree to make for more comfortable viewing. If on Windows, you can see this value by right clicking on the desktop and selecting “Display Settings”. The scaling is governed by the “Scale and Layout” section.
You can set ZBrush to ignore this by right clicking on the ZBrush.exe, and selecting “Properties”. In the Compatibility tab, click “Change High DPI settings”. In the next menu, enable "High DPI Scaling Override and make sure the berhavior is set to “Application Controlled”.
ZBrush will now ignore your OS’s scaling when launched. This will result in ZBrush looking extremely small if launched on a display running at 4k. You can use ZBrush’s own internal scaling functions to increase readability. The primary function for this is Preferences> Interface> UI> Button Size. Scale up the buttons until you find a comfortable size. You will have to restart the program to see the changes take effect. The appearance of the program may differ from what you are used to under the OS scaling.
Take care! 