Control is not the kind of game that ends with its narrative. Many games encourage players to finish every sidequest and narrative line they want to before entering the game's final challenge, tying up the whole game so that credits can roll and the game concludes once the player clears the last hurdle. In Control, there's still lots left to do for Jesse Faden after the end of the game. She might have thwarted the Hiss, but the Bureau of Control still lays in shambles. There's plenty of tasks and chores for her to pick up to help the Bureau get back on its feet, and along the way, there's still lots of Hiss to fight.
Another video game convention that Control stays away from is the final destruction of the protagonist's nemesis. The Hiss are far from gone at the end of Control, in spite of Jesse's efforts. It continues to infiltrate the Bureau, and corrupted agents continue to wreak havoc throughout the Bureau's many labyrinthine departments and floors. Since the Hiss clearly aren't gone, will they be the focus of a potential Control 2? It certainly wouldn't be surprising if the Hiss returns with a vengeance. However, with all the lore that Control put in place, there's also a lot of other potential antagonists on the table.
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Fighting the Hiss isn't just about targeting some specific leader and taking it out so that the whole system falls apart. It's an eldritch and unfathomable force from beyond humanity's reality, so it's not surprising that Jesse can't hope to simply destroy it. The Hiss' survivability and overwhelming power makes it seem reasonable that it will return in Control 2. The question becomes how it will choose to attack. It's possible that it would simply try to destroy the Board again, but it doesn't seem likely that the Hiss would keep trying the same strategies, nor would rehashing the same threat as the first game make a very strong narrative for the sequel. If the Hiss comes back in Control 2, it will probably have new plans.
It might start to target Jesse herself rather than trying to crush the Board or the Bureau on its path to taking over the world. While Jesse might have seemed insignificant to the Hiss once, she has proven herself to be a more than capable opponent to the Hiss' plans. Alternatively, the Hiss might find a way to invade the Earth that doesn't go through the Bureau. That would mean that Control 2 might end up taking place in the streets of New York City, rather than within the Bureau's confines. It's hard to imagine a Control game that takes players outside the Bureau and its attached Thresholds, but it'd certainly be exciting to use Jesse's powers out in the world. If the Hiss were to infiltrate the Earth this way, Remedy Entertainment could create all kinds of exploration opportunities by introducing dimensional gates and warped terrain in New York City's most famous landmarks.
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It's still possible that the Hiss don't become the focus of Control 2. The game puts a frequent and persistent emphasis on the fact that there are countless other planes populated with beings that the Bureau still doesn't understand. For instance, the Mold provides an additional threat throughout Control, acting independently of the Hiss but still causing tons of problems for Jesse and her colleagues. Control 2 might decide to focus on another extraplanar threat, whether it's the Mold or another force that Jesse hasn't seen yet. Control 2 would benefit greatly from letting players look into more worlds, now that the tone and lore of the IP are in place.
However, it seems most likely that the Hiss will remain the main antagonist of Control 2, or at least will be a major part of the game's story, if not the main threat. Jesse's relationship with the Bureau is permanently intertwined with her battle with the Hiss. It defined her experience joining the Bureau, and since it hasn't been destroyed, odds are low that it'll drop off and stop being a part of her life anytime soon. If anything, the dangers of the Hiss might ramp up in Control 2. Now that it knows that there's someone out there that can threaten it, the Hiss might become more dangerous than ever.
Control is available now for PS4, PS5, PC, Switch, Xbox One, and Xbox Series X/S.