Thanos is the ultimate villain; the mad titan eternal is super-strong without any of the Infinity Stones and he is sure to be seen again in MCU. At least 14 Million of him.
It is not only a possibility that Thanos will be back for blood, but it is also a probability. Why, you ask? The answer is simple – The realities that Doctor Strange saw are real. As we know, the name of the next Sorcerer Supreme movie; Doctor Strange 2: Multiverse Madness. The title itself suggests that by the end of it, we could see Doctor Strange dealing with Thanos, who is inevitable. What Kevin plans to do as MCU moves ahead is not very obvious but this reality could be in trouble if connected to the Multiverse.
What does this mean for Thanos?
Thanos clearly states in Avengers: Endgame, “ I am inevitable.”, right before Iron man shows who the papa is. “I am Iron Man.”, is an iconic line and the fact that he sacrifices himself to save the Universe shows how really self-aware Tony is on Earth 616. But maybe all the sorcerer supremes are not as perfect across the Multiverse, not Iron Man. We know that in comics, Captain America has been a part of Hydra.
This offers up the theory that Thanos is proven inevitable in more than two timelines, at the least. Two are deadline from Earth 616 and another from Earth 616 B (which came into being because of time travel taken on by the Avengers team).
Thanos came back from one timeline by tracking down Nebula. There is nothing to say that a similar circumstance leads to the death of all the Avengers in a different Universe. The surviving Thanos, if aware of the Multiverses could possibly wish to ruin it all.
Is Thanos Inevitable?
The reason that Thanos is inevitable in Avengers Endgame is that he is always the one behind the chaos. The same will not be the case through phase IV of MCU. Though Thanos could be a villain in one of the movies as aforementioned.

This phase is going to have someone much more powerful, and like Thanos, not certainly evil. This villain is probably going to be the Celestial, planet consuming being from the previous Universe, Galactus. His Herald, Silver Surfer is bound to be a part of it all.
The MCU Galactus Theory
In Guardians of the Galaxy, we see an Eternal, destroying a planet using the Power stone. It could be so that Galactus in this Universe is focussed on destroying planets with the Celestial seed within them. Why? Because if there are too many of them alive, they can easily destroy the Universe.
So, who is the villain, Galactus or the Celestials? Well, we may get that answer with Marvels Eternals.
Galactus will be the force to drive out the Celestials, saying that the previous statements are true. Silver Surfer could have a run-in with Captain Marvel, establishing the entry of Galactus. Thanos is inevitable because he is the ultimate villain. The same was done with Loki and Thanos but in a very different way. Thanos could also become a threat to the universe again, leading the Celestials to our planet for the purpose of finishing off the heroes trying to save it all.

Galactus would be the good guy, stopping the Celestials. The part that comes into play for making Galactus the main villain? Galactus must destroy Earth lest it turns into a celestial being.
Is this a plausible Theory?
There may be a few loopholes in the theory but the possibility of a similar storyline taking place in the MCU Phase IV is a big possibility.
