Since Zero Time Dilemma is coming out for the 3DS and Vita next year, I decided to actually state what I think is going to happen in the game. So without further ado here we go.
1) The game is going to take place over the course of seven days, I think it will have different puzzles for different days. This will make it so that they could expand on the endings and make them much longer and also include more character interactions. I think by the fourth day, a least one subject will show symptoms of the Radical 6 virus. Since Day 7 is when the virus is supposed to be released. This is also when Sigma is supposed to lose his eye and his arms.
2) The artwork that was shown in the Ax 2015 expo in July displays Sigma tied to a chair and having a gun pointed at his head, this is presumably when Sigma is going to lose his eye. But who is the woman in the picture? I don't think that it is Diana, because why would Sigma create Luna from someone who tried to kill him? But the assumption is that it is her because of the bluebird necklace. We don't even know how Sigma obtains it, but I think that he probably took Diana's place in the chair, because he cares about her. Somehow, Sigma manages to escape in this timeline and kills the woman, probably with the gun and takes the Bluebird pendant. Diana also probably tells him to keep it for saving her life. Also I noticed the gun looks very similar to the revolver from 999, I don't know if it is the same one or if it is different. As for the woman's identity, she is probably a new character, because the hair doesn't even look similar to Luna and Luna is supposed to be a replica of Diana.
3) The use of Radical 6. In Tenmyouji's ending, Tenmyouji states that the virus could have been an intentional part of the simulation, that is what I believe also. NASA in the Zero Escape universe probably discovered Radical 6 somehow and decided to use it in the Mars test simulation. I looked up the gravity on Mars and it is significantly lower than Earth's. I remember that Radical 6 was used to mask the fact that they were on the moon in VLR. The Radical 6 is probably used to make the simulation as accurate to Mars as possible. However the thing that no one knows at this point is that it causes people to kill themselves. Free The Soul is probably involved with the simulation and has plans to release the substance since it could be similar to the "Cancer cure" in the game "One Chance".
4) As for who is going to appear in this game, I think everyone is from 999 and VLR. Some characters more than others. The only ones who won't are Quark and the 9th man, at least not directly. But we do know that Santa is going to appear for sure.
I will discuss more details later.