The game handles exactly like the handheld Mario RPGs that came before it -- the A and B buttons control the actions of Mario and Luigi, respectively. You walk them around a 2D platform world filled with monsters who engage the plumbers in turn-based combat. Combat cues are timing-centric -- pressing the right button mid-jump gives you a boost of power, and rhythmic button presses let you bounce Koopa shells off enemies for massive damage.
However, Inside Story flips the script on the franchise, introducing an gameplay and story convention that is nothing less than brilliant in an Innerspace-esque kind of way.
See, your two mustachioed heroes are doing the bulk of their familiar 2D adventuring inside Bowser's body (hence the name), while Bowser himself will be embarking on his own adventure, presented in an isometric, Super Mario RPG-esque fashion. Just as you had to control Mario, Luigi and their baby counterparts simultaneously in Partners in Time, you'll be controlling Mario, Luigi and their overworld/adversary Bowser simultaneously in Inside Story.
This gameplay function works both ways -- a long hallway features bone fragments that serve as barriers to the Mario bros' progress. Forcing Bowser to drink water until he feels "all sloshy" fills the chamber, causing the bones to float safely out of the way.
We can't wait to see how these two different worlds interweave. As evidenced by the series' extremely pithy dialogue, the game's creators are probably clever enough to come up with a number of scenarios where the miniscule plumbers and dino-turtle-monster have to work together. Combining said cleverness with the series' tried and true action-oriented RPG gameplay is going to create what could be the most entertaining chapter in an already entertaining series.
We're just hoping Mario and Luigi's internal exploration doesn't go south, if you know what we mean.