Ahead of Avengers: Infinity War, Thanos made a handful of cameo appearances throughout the MCU, setting the stage for him to take on Earth's Mightiest Heroes. The first came at the end of The Avengers in 2012, a strong indication that Marvel Studios had long-term plans for the Mad Titan.
The villain's story reached its end in Avengers: Endgame when he died. Twice. However, we've since seen a Thanos Variant in What If...?, and Josh Brolin has now talked more about potentially reprising the role in live-action. "[Marvel Studios has] their own trajectory that they're worrying about and if they want me to do it, I would do it I'm sure, but I don't know what they're thinking."
"I don't know what their plan is," the actor continued. "We've kind of bookended this thing after 10 years. I was so happy and I loved being involved in that so much because that wasn't the intention when I first got involved." Brolin not being sure what comes next isn't a surprise, and while we could see Thanos again, you have to believe it probably won't be for a while yet.
Assuming we get an Eternals sequel, it would make sense for Thanos to appear in flashbacks. Aside from that, the MCU appears to be moving on to a new big bad in Kang the Conqueror.
Regardless, Brolin would add: "The whole Thanos character, it was more of a cameo and they liked the character so much. They had never felt like they had a villain that was substantial enough for what they were creating and then I think they felt like they found it and then there were two movies that kind of revolved around it. It was a lot of fun and it worked out for them very nicely."
In the comic books, Thanos frequently returns after being defeated and has died and been resurrected on countless occasions. In the MCU, we'd argue that his story has reached a natural conclusion, but if Brolin does want to return to the MCU, there's always Cable in Deadpool 3, right?