I løbet af The Callisto Protocol kommer du til at samle en masse våben op, og disse kan du naturligvis opgradere løbende. Samtidig kommer der til at være mangel på ammunition, så du kommer til at skulle indgå i nærkamp løbende.
I et interview med Game Informer slår studiet fast, at den hedder "half melee, half ranged":
"We're in equal parts a melee and ranged game. What we want out of that is that you engage guys close up and then as you gain distance you use your guns and weapons on them. We also have what we call the GRP, which is a guards restraint device. What that will do is hold guys. You can grab them, pick them up, push them away, pull them towards you for all sorts of things. Once you get your hands on it, you get to have a little bit more fun."
Du kan se en trailer der demonstrerer det her: