Daan Wijffels summarizing the necessary steps to enable Spatial Audio on Plex:
Meet custom profiles in Plex! These profiles allow us to change which codecs are sent to a certain type of device. So al (sic!) we have to do is create a profile XML file with the right information and voilà… Spatial Audio!
If you’re running your own Plex server you can rather easily enable Apple’s Spatial Audio. On the client, iPhone or iPad, you’ll have to enable the old Plex video player (Settings > Advanced > Use Old Video Player). For those interested in additional details, these steps and requirements were previously listed on Plex’s official forum.
Apple introduced Spatial Audio with iOS 14. The surround sound can be activated on AirPods Pro (starting with firmware 3A283) and AirPods Max in iPhone and iPad. Apple lists the necessary iOS/iPadOS hardware in a support document.