I'm very experienced with the Harmony line, but don't have a Smart TV. However, I'd expect it's the same as setting up the Harmony for any multimedia device like a streamer. You'll get an assortment of commands to do pretty much everything that's on the original remote, minus of course things that may be handled by proprietary RF or Bluetooth, such as mouse and keyboard functions.

I wouldn't anticipate any problems setting up a Harmony for any of the current TVs, with the caveat that the owner may need to use the original remote as a keyboard if so-equipped and required.