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Weiss is the leader of The Tsivets of Deepground, a group of superhuman beings more powerful than those affiliated with SOLDIER.
When Genesis Rhapsodos was defeated by Zack Fair, Weiss and his brother Nero retrieved Genesis' body and took off with it in a helicopter. Though neither Weiss or his brother had ever seen Genesis before they knew that they along with all the other Tsviests were spliced with his genes.
When it was revealed that Genesis had not been killed by Zack, Weiss and Nero attempted to convince Genesis to join their rebellion against The Restrictors, the former masters of Deepground, but their offer ended up being refused by Genesis who would go on to seal himself in a cavern deep beneath Midgar.
At some point later on, The Restrictors decided to permanently chain Weiss to a throne that was connected to Mako Reactor 0 so that he would never be able to overthrow The Restrictors. When he was given two brand new gunblades, Weiss challenged one of The Restrictors to a handicapped fight in an attempt to prove that he was superior to them all.
The Restrictor said that he would be allowed to fight handicapped but would do so against Azul the Cerulean and Rosso the Crimson whom he was able to overpower both in their natural states and in their Arch Azul and Bloodthirst Rosso states. Because he was unable to attack the Restrictor, Weiss ordered an unnamed amnesiac female Tsviet to shoot the Restrictor and eventually was forced to engage him in a vicious fight.
The Tsviet eventually defeated the Restrictor only to find herself being stabbed in the stomach by Weiss. Weiss then turned on the Restrictor and slew him. During the time of the revival festival in Kalm, the worldwide network that had been wrecked during the Meteor Crisis was finally restored. Infected with a time-released virus that was meant to control him and kill him after a three day period if The Restrictors signal were to disappear after he had overthrown The Restrictors, Weiss was performing a Synaptic Net Dive and ended up being taken over by the mind of Professor Hojo.
Hojo, whom had placed his mind within the worldwide network just prior to his death, began ordering Deepground to abduct those who had not been infected by the Geostigma plague so that they could serve as incubators of enough pure mako that would allow Weiss' body to absorb the Omega entity once he tricked the planet into summoning it.
Weiss' powers were increased astronomically by the mako he had absorbed, allowing him to easily overpower individuals such as Vincent Valentine. However, during their fight Vincent would eventually turn the tables on Weiss/Hojo by using the power of Chaos. When Weiss was defeated, his brother Nero, who had been watching the whole fight wanted to merge with his brother and began approaching him.
Hojo, who knew that if an "impure" being such as Nero merged with Weiss' body he would not be able to control the Omega entity anymore, demanded that Nero stop. But both Nero and Weiss refused to listen to the madman's pleas and merged into one entity, which resulted in Hojo being finally destroyed once and for all as the two brothers underwent the integration process.
Weiss, on a sense of compulsion, then invoked Omega's power and vanished in a ball of light while Omega itself manifested over Midgar. Weiss was defeated by Vincent once more after his Chaos powers had been dramatically increased by the soul of Lucrecia Crescent. A short time after Omega had been destroyed Weiss' corpse was found by a reawakened Genesis Rhapsodos. As Genesis walked off with Weiss' corpse he told him that there was still much work to be done.