the most common problems are the following:
The bad news is that both of these relate to bugs in Mac OS itself. The good news is that there is an easy fix when this happens
Setting the wallpaper is actually a very simple command in Mac OS. Essentially - I say 'set this image for screen N'
Once that is done - Multi Monitor Wallpaper has no part in 'keeping the wallpaper active', so when the wallpaper is 'lost' - that means that the operating system failed to properly save and restore the configuration. In some cases, the system gets 'stuck' and stops allowing apps like Multi Monitor Wallpaper to set new wallpapers.
I have pinned down at least one way to reliably re-create this bug on my mac. What seems to happen is that the database where the system stores what image is applied for each screen/space gets corrupted.*
The easy workaround is simply to delete the system database which stores the currently applied wallpapers.
To do this:
This will reset all your spaces/desktops (though you won't immediately see the change in your currently visible workspace)
Once you have done this, you can set your wallpapers with MMW again
For the techincal: The database is stored at ~/Library/Application Support/Dock/desktoppicture.db