This original question was about a specific instance:
A self-published book is picked up by a traditional publisher, will they assign a new ISBN?

The short answer is yes. They will make it a new edition with new content or a new cover and release the book under a new ISBN that they own the metadata to and handle all incoming royalties.

The bigger question behind this question is, how likely is this to happen. I should probably do a whole video on this. But given the number of authors who self-publish and the number who are successful enough in terms of sales and royalties to attract the attention of a publisher or agent, the odds are slim. You have to put your hat in the ring. And likely with a new book. And then the backlist could be on the table.

My agent and I discussed this as some of our initial conversations. We decided, let’s get this new book a deal and then we can look at subsidiary rights deals for the back list (translations, TV/film, etc.)

Yes, we can all name the big names who made a huge leap from self-pub to trad pub. But this switch should be strategic and you need to make a business case for why a traditional publisher should pick up your book.