The Sequel Trilogy has been a bit of a PR disaster for Disney and Lucasfilm. It's well known that fan reception of the films has been incredibly mixed. On one side, there are those who fight to defend the trilogy tooth and nail, contrasted by those with a deep disdain for the creative decisions made for the story.
Mark Hamill's displeasure with the treatment of Luke Skywalker has been well-documented by this point. Prior to the release of The Rise of Skywalker, fellow co-star John Boyega voiced his own unhappiness with The Last Jedi, as did Daisy Ridley. Boyega has since gone on social media on multiple occasions after Episode IX and claimed he likely wouldn't return to Star Wars, a sentiment now shared by his Resistance pilot friend...
During a Deadline panel via Indie Wire, Oscar Isaac said he would likely never return to Star Wars:
"Probably, but who knows. If I need another house or something."
Isaac explained that his goal as an actor was never to helm big blockbusters, but to tell personal stories with those he admired:
"It’s not really what I set out to do. What I set out to do was to make handmade movies, and to work with people that inspire me."
The actor also made sure to note that he enjoyed his time working on the Sequel Trilogy:
"I enjoyed the challenge of those films and working with a very large group of incredible artists and actors, prop makers, set designers, and all that was really fun."
WHAT THIS MEANS
In layman's terms, he's probably not coming back. Many fans were extremely unhappy with the decisions made for the Sequel Trilogy, and several members of the cast clearly share similar feelings. Hamill, Boyega, and Isaac have all taken shots at the new films in the past but walked back their comments later on (likely due to phone calls from The Mouse).
This is always a difficult topic to discuss because there are many fans who did enjoy the Sequel Trilogy, even if others and some of the actors didn't. The criticisms levied against the new films hold a great deal of validity, and certainly, Disney and Lucasfilm could've strived to produce something that better continued the story George Lucas told. Still, these films will always a place in the hearts of the new generations of fans, and some of the old.
One of Oscar Isaac's major gripes with the trilogy was the rejected concept of the "FinnPoe" fandom ship by Disney in favor of a romantic backstory with Keri Russel's Zorii Bliss and a retconned spice-smuggling past. Both parties brought up valid points for their positions, but like with Hamill and Boyega, the rift has already occurred.
Despite Isaac's comments, we can never say never about the chance for his return to the role of Poe Dameron. It's grueling work to play a physical lead role in a Star Wars trilogy, and the recent one only just wrapped up. In a decade or two, with the right story and director at the helm, anything is possible. Maybe someday the new gang will get back together...