Moody Ben Blue, chubby Hi Stolowitski, geeky Shelton Devers and supersmart Tory Brennan possess unique abilities resulting from a scientific accident with a super virus. In the first book, the virus inserted canine DNA into their DNA, and now they form something resembling a wolf pack, with acute senses and animal urges for hunting and fighting. When they go "viral," their brains "snap," their eyes glow, and their senses become highly acute. They call it flaring. Tory, 14, is the youngest yet dominant force in the pack, and she has an extra sense, being able to read the minds of others, even Coop, her wolfdog — the fifth member of the pack — but only when the other person is in close proximity to her. Tory meets her father, Kit, for the first time, after her mother is killed in a car accident.
Loggerhead Island, off the coast of South Carolina, houses a veterinary research facility (LIRI) where the parents of the four work. Kit is the director of LIRI, where the four contracted the virus while breaking into a lab to rescue Coop, who also has the virus. The kids like to hang out on Loggerhead because it is secluded, and it gives them a chance to experiment with their new powers, which they've managed to keep secret from just about everyone, even their parents. One afternoon, they uncover a geocache puzzle box.
At their secret bunker on another unfrequented island, the kids work on opening the puzzle box. Once opened, they find a letter written in code and signed by the Gamemaster. Hi's experience with geocaching tells him that the planter of this box does not play by the rules. But the kids are drawn into the mystery and the challenge of breaking the code that leads to more clues.
As they follow the clues, each with an assigned deadline, they realize that they are dealing with a madman. They find they are entangled in a crazy game that may result in a hidden bomb killing innocent people if they refuse to play or if they don't follow the rules of the Gamemaster. One of the rules is that they are not to tell anyone.
They do what the Gamemaster says, but at the same time, they resolve to find him. The clues and research lead them to a castle, a golf course, a shooting range and a monastery's cemetery. Inside the cemetery that their parents forbid them to enter, they follow the clue into a mausoleum and find a sarcophagus. They open the sarcophagus and see a dead man who has not been dead very long. The teens would like to tell the authorities, but the Gamemaster reminds them (via messages on an iPad he has left for them) that the lives of others are at stake if they do. The note hidden with the corpse is even more threatening, and with it are pictures of them and their families, indicating that the Gamemaster is always watching and knows their schedules. The final clue is set for Friday at 9 p.m., coinciding with the time Tory will debut at a cotillion. They deduce that the Gamemaster has planned a disaster to occur during the cotillion.
Tory is the first debutante presented at the ball, held at an old castle. After her presentation, she joins her friends to focus on finding the device the Gamemaster has planted. They notice familiar clues hanging in the castle that lead them to the lowest level and into an interior room that holds the ventilation systems. They locate the device that they thought would be something explosive. Instead it is a box with a valve that releases bromomethane, a poisonous gas. Turned to the right, the fumes will travel into air ducts that connect to the ballroom and poison hundreds of attendees. Turned to the left, the gas will fill the room where they are now trapped by a steel gate. Unable to open the gate to freedom, Tory decides to turn the valve to the left to save the lives of everyone in the ballroom. Then she and her friends close themselves off in a passageway, using Hi's jacket to help block some of the bromomethane that is filling the ventilation room. The four flare, and then use their super-human strength to raise the gate enough to escape.
Still with an urgency to find the Gamemaster before he kills again, the four teens focus their thoughts on known facts while preparing for a Category 4 hurricane forecast to hit the area. They have orders to evacuate. From a friend, they learn that the ballistics expert they met earlier at the shooting range was an impersonator. The real ballistics expert had gone missing, and they realize from the description that he was the body they found in the sarcophagus. The kids decide to brave the hurricane and go into the deserted city of Charleston to search for the Gamemaster. Ben remembered a G parking sticker on the oversized pickup the impersonator drove to the shooting range. The G parking decal is assigned to a four-block radius in Charleston, so they are sure they can locate the pickup and the Gamemaster. They find his truck and house and manage to get inside. But the Gamemaster gets away. Before he does, he leaves the fireplace burning and a gas line severed. The kids get out just before the house explodes. They continue their pursuit of the Gamemaster into the city square, just as the eye of the hurricane passes over. The Gamemaster is armed and shoots at them, grazing Tory's arm. Like the pack they are, they work to encircle him at a distance as he continues shooting. Hi and Coop begin to charge him from behind, then surprisingly Kit shows up and takes a swing, followed by Coop who knocks the Gamemaster down and Tory who kicks him into unconsciousness.
While the worst of the storm finishes its destruction, the group shelters at the hospital because it has a generator. Tory is shocked to learn that Ben initially had worked with the Gamemaster in setting up what he thought would be a fun time for the group following clues and solving puzzles. When things became dangerous, he was unable to stop the events the Gamemaster had set in motion. From the police, they learn that the Gamemaster was a veteran and a former munitions expert who suffered from post-traumatic stress disorder. The kids face a trial, with Ben as the star witness. Their school expels Ben. Tory struggles with her inability to forgive Ben, because she thinks he should have told them of his involvement with the Gamemaster. She has a flash drive Ben found earlier in one of the LIRI labs, and she hopes it will uncover some of the mystery of their viral condition. Since the hurricane, Tory notices that she feels a connection to the rest of the pack even when she isn't flaring.
The book concludes with one of the pack's classmates fingering the top-secret research papers of the scientist who was responsible for development of the super virus. He suspects there is something unusual about the four friends, and he intends to unlock their secret.