Joe Ledger and the DMS (Department of Military Sciences) go up against two competing groups of geneticists...
One side is creating exotic transgenic monsters and genetically enhanced mercenaries armies; the other is using twenty-first-century technology to continue the Nazi Master Race program begun by Joseph Mengele. Both sides want to see the DMS destroyed, and they've drawn first blood. Neither side is prepared for Joe Ledger as he leads echo team to war under a black flag.
The story starts three months after the events of Patient Zero. Joe Ledger and Echo Team has run a number of missions for the DMS, terrorists cells closed, assassination attempts thwarted, and the like. Joe is visiting the grave of his former girlfriend, Helen, when he is approached by NSA agents. Under the orders of the Vice President, while the President is in heart surgery, they are attempting to seize control of all DMS staff, properties, and equipment. DMS teams and facilities are trying to keep their control, using threats and dissuasion. Joe ditches his tails and gets the info from Church. Jigsaw team has gone dark, and they’ve received a weird email from an unknown source. Joe is sent to Denver to find out what happened.
Cyrus Jakoby, and his assistant Otto, are brilliant geneticists. They are celebrating their greatest achievement yet: in one week, the extinction wave will begin, and all of the mud people of earth will be dead. Paris Jakoby, and his sister Hecate, god-like specimens of beauty and genius geneticists in their own right are pushing their own agenda: making billions of dollars and standing on top of the world.
While Joe was visiting Helen and escaping the NSA, the rest of echo team is approaching a man hiding out in a rundown hotel. It was a routine pick-up turned bad as their newest addition, Big Bob Farraday, got half his body shot up by Russians with automatics; Bunny and Top take them out. Church contacts them and fills them in in a hurry, they must leave and move fast to avoid the NSA and rendezvous with Captain Ledger in Denver for backup.
Church informs Joe that Captain Peterson and Jigsaw team has gone dark on a mission in a storage facility called Deep Iron in Denver. Maybe NSA got to them but he doesn’t think so, he wants Joe and echo team to find out. Church also contacts Linden Brierly, and uses a Presidential Alert protocol to make him wake up the president from his surgical recovery as soon as possible and put an end to the Vise Presidents coupe. He reaches out to the President's wife, who has tremendous respect for Joe Ledger since he saved her life at the Liberty Bell zombie outbreak. She agrees to help them out.
On the flight to Deep Iron, Joe video-conferences with Dr. Hu and Church and is shown a video from the unknown email of a hunting party tracking and shooting a real-life unicorn, very poor audio but the video was clear. Hu and his team verify its legitimacy. The video was sent by an anonymous person in an old email account held by Church. Church recognizes one man from the video, Gunnar Heckel, who should not be alive. Heckel was involved in a group called the Cabal. The Cabal was an evil group active during the later years of the Cold War, bent on ethnic cleansing and was behind racial conflicts over last half of the 20th century. A younger Church, apart of a group known as The List, systematically took apart the Cabal and everything they had created. Seeing Heckel in the video, they think someone has re-formed the Cabal and is picking up where they left off. Heckel’s family had a storage unit of information inside Deep Iron, and Echo team must retrieve it.
Upon landing on an airfield near Deep Iron, echo team meets up with Brick Anderson. Brick is a DMS soldier with an artificial leg driving a Mr. Softee truck which is also a rolling arsenal. He drives echo team to Deep Iron and guards the entrance while they make they way down to the lowest parts of the facility, wishing for back-up, but with the NSA hounding down all of their agents none can be provided. Moving to their destination, where Jigsaw team was headed looking for Gunner Heckels data storage, Echo encounters blood, lots of it. There are Deep Iron staff and Russian special forces torn to pieces; some still alive to put up a fight. Finally reaching their destination, they are ambushed by two huge berserkers: modified super soldiers, ape DNA and other sorts added to their genes to be stronger, fiercer, and more aggressive. Overpowering Top and Bunny, Joe is fighting quick and smart, with his rapid release knife and going for the head and face, its only vulnerable parts. The berserkers run off injured, but they got what they come for; although echo has a lot more of Heckels data they can comb through to find answers. The DMS brings in Jerry Spencer to go through the crime scene to uncover any data they can salvage. Spencer uncovers many documents and also the remains of Jigsaw team, who has been killed. The papers are revealed to be medical data and horrible experiments: pain and endurance testing on human beings in the nazi camps, performed by Joseph Mengele.
The President wakes up, very pissed off, reams out the VP for his actions, and the DMS is able to get its backup and resources they desperately need. Rudy is sent to the Hub, DMS’s Denver site, to talk through the recent events and the loss of Jigsaw. The twins lost their tie to the VP, they have been manipulating events to try and acquire MindReader from Church and the DMS to further the progress of their own research.
Back at the warehouse Joe, Grace, Hu, and Bug go over all the new data and recent events. Friends of Church from The List have been killed over the last few months. When they first killed off the Cabal, Church acquired Pangea, a software package they used to steal research around the world without a trace. Church later upgraded and added functionality, it is now known as MindReader. He and Aunt Sally are the last surviving members of the List. The team discusses Mengele's work and the data recovered from Heckle’s bin at Deep Iron. But are at a loss as to what may be going on.
The team is interrupted by another email, sent by a kid, who sent the previous email with the unicorn video. The kid is using video chat this time to get his message across, he is trying to reach Church and get his help to stop the bad men. He explains the horrible plans that are about to commence and the location of the bioweapons factory called The Hive.
Echo team rolls out to his location, to make contact and retrieve him and any information he has. The kid helps them in, but they hit heavy resilience against guards and modified creatures called Tiger Hounds: giant fierce dog beasts. Echo team acquires the kid and saves a strange group of people called the New Men, although with every new bit of info they recover their hatred increases. Unable to get info from their computer drives, Joe Ledger forces the information out of the guard, Carteret, by slapping him into submission. Church and Bug discover the extinction wave plans. Backup clears the island of remaining enemies and Joe and Grace can get back into each other's arms.
Cyrus and Otto, always at odds with the twins Paris and Hecate, not knowing where their Dragon Factory is, putting up with their disrespect, are tricked into believing their treachery because of the DMS attack in the Hive. They make plans on attacking the Factory with their Russian mercenary army, killing at least one of them, and acquiring all of their research. Their personal assassin, Conrad Vader, will join them. Vader has been on the hunt for surviving members of The List for the past few months, to clear the road for the ne Cabals plans.
The DMS has taken in the kid, although he doesn’t feel at home anywhere. Church is looking through reports, the kids DNA and fingerprints are a match to Gunnar Heckel and Hans Gruber. With the information the kid provided, and what they got out of Carterette, they realize the scope of their problems. This is a global ethnic cleansing happening, and they need to stop it. They might have caught it sooner if not for all of the NSA slowing them down. DMS locates another facility, the Deck, and moves in, but as the are moving in, Cyrus and Otto are being picked up by the twins to be taken to their facility, the Dragon Factory. Joe and echo search through the Deck while Grace and alpha head to the Dragon Factory and take it before echo arrives.
In the factory, the twins are giving a tour to Cyrus and his group, culminating at the Chamber of Myth, a room of their most fantastic creatures. Cyrus surprises the twins by killing their little dragon and unveiling his grand plans, admitting his disappointment in them, while his soviet team attacks the island. Grace and alpha team are attacking the island as well. Cyrus unveils the extinction wave to them and who he really is; after many plans over the previous decades, he, Joseph Mengele, still alive after finding the anti-aging gene, has the extinction wave set to play.
Alarms sound and grace is separated as she dives into chamber after the group, wanting to get the trigger device that will launch the extinction wave in the coming hours. The whole island is hit by an EMP to stop them from launching the wave, but also cutting down all their team's electronics. Joe and echo race to catch up to alpha and grace, cutting through soviets, berserkers, and other mutations on the island. Cyrus group makes their way to Hecate’s office, where she has a computer unaffected by the EMP so they can start the wave. Grace follows in pursuit, and Joe is trying to catch up to help. The rest of echo is backing up DMS teams and catching up further behind.
Grace Courtland bursts into the office and shoots down everybody, but not before Cyrus was able to get the Go-Order out. Still alive, Cyrus as the abort sequence, but before Grace could make him say it, she is shot in the back by Conrad Vader and dies in Joe’s arms. Joe snaps inside of his own head. Conrad Vader escapes as Joe is forced to stay to ferociously kill the remaining berserkers and get the abort codes from Cyrus, which he does, at great and painful lengths put on Cyrus Jakoby.
They had successfully stopped the global attack. Joe spends weeks in the hospital recovering, reflecting on what happened. Thousands turn out to Grace’s funeral, she was a celebrity who had saved the world. The teams working with the Jakobys’ to release pathogens were hunted down and dismantled by the DMS and local officials. Joe is done with hunting evil, he is tired and worn out. He quits the DMS. And on his way out, has a folder from Church, containing the recent location and relevant info on Conrad Vader.