I am trying to display some KPIs on a monitor on the shop floor. I have a PC that is used constantly by everyone, to which I have attached a second screen. I have opened my PowerPoint presentation on the second screen and set it up on a continuous loop. This works well until someone uses the main screen, causing the PowerPoint on the second screen to pause. If no one unpauses it, it stays on the current slide. Is there a setting I can use to play the presentation on the second screen without it pausing when someone uses the main monitor?

Sounds like a neat idea to keep your team informed. If I am being fully honest and this is coming from someone who has used PowerPoint presentations with hundreds of slides and experienced pausing and many other things. You want this computer that everyone is using to be able to easily play this presentation with no issues. To do that you need minimize the computer resources to really prevent the pausing. There are 2 things you can do.
Since you asked for a setting. there is one. If you set the show type to browse by individual it does not allow them to access the other part of the PowerPoint application causing the pause
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I cant seem to insert a screenshot ok.
So thats Slide Show > Set Up Slide Show > Check Browsed By Individual
Ensure Loop unti ESC is selected
Move the Powerpoint application to the screen you want it to show and then press F5 to start the show.

Option 2 which I think will be a better fit.
Go to file > Export > Create Video. Make a video of the presentation and then play it in something like VLC player with full screen enabled. Set a loop. The computer will have no problem playing a video over and over again but a PowerPoint constantly running might cause some delay.

Give these a shot and let me if it fixes the issue.

Thank you so much for the feed back, i will have a go and see if it works. I will keep you posted.