She'll be back in the game no problem , but not as she was before , she'll be in the forerunner system or have become some super AI , or something like that , I can see the chief going lone wolf in the next game (halo5) since its suppose to be a dark game , but I doubt they will remove her completely ,
Im afraid that 343 will do something silly with the lore like have more stupid space magic in the game, it broke me to see cortana "die" but I'm sure she'll be back , wheather she will be the same that is the question