Cole & his friend,Zeke meets with NSA agent Lucy Kuo,who informs them that Wolfe, the man who created a Ray Sphere,has developed a stronger design that could stop the Beast. Before they head to Wolfe's lab,The Beast attacks the city. Cole tries to stop him,but gets overpowered and Empire City is completely destroyed.
Arriving in New Marais,Cole & his allies learn that energy magnate Joseph Bertrand III, an anti-Conduit demagogue,has seized control of the city. Cole rescue Wolfe and learns that he invented the Ray Field Inhibitor,also called the RFI,a device capable of stripping Conduits of their powers. Bertrand's private army,the Militia attacks,killing Wolfe and capturing Kuo.
Cole & Zeke meet Roscoe Laroche,a Vietnam veteran who lead the resistance against Bertrand,and Nix,a Conduit with the ability to manipulate and ignite napalm like substance. They quickly freed Kuo,who turned out to be a Conduit who has been forced to transfer Ice powers to generate mercenaries controlled by Bertrand. Cole discovers Bertrand,who is also a Conduit, has been transforming kidnapped civilians into mutant monsters to terrorize the people into supporting him. By the time Cole confronts him,Bertrand transforms into a giant monster before the Beast arrives.
After Bertrand was killed,The Beast turns out to be John White,who thought had died in the process of destroying the first Ray Sphere. He tells Cole that humanity is perishing from a plague born of the radiation from the Empire City Incident. As the Conduits are immune,White uses his newfound powers to activate the Conduit gene in plague victims. After locating and absorbing the last core,Cole prepares to activate the RFI,only to realize that it could not only cure the plague,but could kill every Conduit,including the Beast. Kuo abandons humanity out of fear & sides with White while Nix sides with humanity since she will no longer be unique in a world of conduits.
Zeke wishes Cole farewell while Laroche & his followers sacrifice themselves to hold back the Beast. Nix sacrificed herself as well,injuring the Beast and allowing Cole to supercharge his powers to defeat him. The Guilt-ridden Kuo tells Cole to carry out as he activates the device,killing himself,Kuo,the Beast,& the thousands of Conduits,and erasing the plague. Everyone honor Cole's heroism & sacrifice.