I could imagine Game Freak design a region based on the Great Lake region or the Washington DC area to connect to the Unova region, something like Kanto and Johto. If it's not a neighboring region but a region that draws inspiration from a particular region in the US, the most probable candidates I could think of are: Florida, California, Washington (where the Nintendo of America HQ is), or Hawaii/Alaska.
The USA isn't the only possibility, there are 3 other possible avenues for Game Freak to choose from. Game Freak could decide to go back to Japan, which has 2 (or even 3) potential regions left. Game Freak also has the option of taking inspiration from other countries/continents like England, Australia, China, etc. Another possibility is to completely make up a region with no inspiration drawn from a real-life region, but I think that's the least likely to happen because there are so many real-life regions to take inspiration from.