The book begins with with Jack having turned Meredith into a genetic vampire. She escapes though but begins to get the craving for human blood. Damon and Elena both desire vengeance on Jack for killing stefan, so they spend much of the book trying to figure out how to kill him. Damon notices how they are strong and fast but not as much as him. But they are unkillable. Damon fights Jack and realizes Jack is somehow stronger than his own creations despite being a genetic vampire. Damon loses the fight, but finds out snapping their necks will neutralize them for a while. Meredith continues to hunger for blood and Alaric notices something is wrong with her but she refuses to tell him. Matt reveals he has a nice normal human girlfriend named Jasmine to replace after Chloes death.
She accepts everything about him. She is also revealed to be a doctor/scientist later in the book which helps to damon and elenas advantage. The guardian Myea comes to elena telling her she has to track down and kill an old vampire named Chivean. Elena tries but fails to find her a few times. She also attempts to come in contact to stefan through bonnies help but fails twice. Damon decides to send Meredith to join Jacks gang to gain info on how to kill him and his creations. Meredith joins and Jack takes her in. Jack, Meredith and 4 other genetic vampires, Adam, Nick, Conrad and Sadie go and hunt down a pack of vampires in which Jack kills the oldest members.Jack tells Nick to find "her" and after he fails, he stabs Nick as a warning to make sure he does it right next time.
Its revealed by Jack to Meredith that the only way to kill one of them is by stabbing them in the back of the head with a scar thats the result of his experiments and that should kill them. She takes this info back to Damon who has captured one of jacks creations and has been torturing him with different ways to kill a vampire. Damon stabs the vampire in his scar but its revealed it only angers and hurts him. Jack comes in and reveals he gave meredith this false info to test her and she fails. Jack and his creations battle damon and friends, frees his prisoner and leaves. Later after the loss, Alaric returns with some info, talking about how Jacks experiments go back to zurich back 5 years ago. He also says Jack has been a vampire for 3 years and his real name is not Jack Daltrey as it was revealed earlier in the book but actually Henry Guch.
Damon and Elena figure out a new way to kill Jack. Bonnie is then found out by Zander whom he and his pack stay clear for the most part of battling jack and his creations. He seems to be really distant and worried. Zander then proposes to Bonnie to marry him and asks her to come to Colorado to join him and his pack but she refuses saying her friends need her here to deal with Jack. He then breaks up with her. However later on, she does accept his marriage and says after she is done helping her friends with Jack, that she will join him and his pack. Jasmine does some resarch in her lab and compares Damons blood to the blood of one of Jacks creations. She reveals that they are almost exactly alike and that vampire blood was used to create his vampires. Later on, Matt goes to Jasmines apartment and tells Matt he has kidnapped Jasmine and will return her if Matt brings Damon to him. Matt decides to trade his life for Jasmine in which Jack accepts. Damon and Elena eventually do find Chivean through a spell from Bonnie using the genetic vampire blood.
Chievean is the vampire whom Jack used to make his creations. Its revealed that she loved Jack but he loved someone else, so she kills his lab assistant and killed his lover and swears to kill Jack. She reveals the only thing that can kill him is this blue poison from a vial only she has on her. They go to Dalcrest College to confont and kill Jack. Damon battles him and stabs him with the vial but its revealed to make him stronger and that Chievean tricked them and actually loves Jack. Elena then kills Chivean as she was going to originally do after they were done needing her. Jack escapes. Jack earlier on stated that he did create a backdoor to his creations and even they werent truly immortal. Damon and Elena go back to Zurich to go through his lab since that is where they found his notebook. Elena and Damon bond and end up kissing. Elena goes to a guard in which the lab is located, she finds out she can compel vampires as he is one of the genetic vampires but it will only work as she doesnt break concentrations. Through a series of events, she finds a black box of 6 vials of blue poison and realizes this is the poison. She uses it on the guard which it kills him. Jack ends up having gone to Zurich as well.
Jack and Damon end up fighting, Elena uses his guardian powers to help Damon fight off Jack. Damon, who is nearly killed by Jack, ends up taking one of the blue poison vials and stabs it into Jacks neck. Jack as he lays dying, tells Damon and Elena he only made his creations cause Chievean killed his lover and he wanted revenge on her and her race, so he made his own vampires and when he was done killing the magical vampires, he was going to kill his own creations. Elena and Damon seem to have no pity for him and he finally dies. Weeks later, Zander ends up marrying Bonnie. Alaric rejects a cup of water that can make him immortal to be with Meredith forever. He vows to find a cure to cure her vampirism. Later on, Elena goes to her childhood home, the place Stefan had planned for her. She goes in only to find Stefan. Stefan reveals his spirit was waiting for her in the house. They have one final kiss and part ways forever.
Damon and Elena go to Paris but Elena begins to choke. Myea the guardian, goes to them stating that because Damon killed a human(she states Jack was a human even if he used science to make himself vampire), the bond between him and Elena is broken and that she will die. Myea leaves and Damon vows to save Elena no matter what it takes. The Book ends.