In the year 2009, a genetically enhanced, 9-year old female (whom creator James Cameron refers to as "transgenic") super-soldier who calls herself Max Guevara, (also known as X5-452, a truncation of her barcode tattoo on the back of her neck 332960013452), escapes along with eleven others like her from a secret government institution. At the institution, codenamed Manticore, they were created and subsequently raised and trained to be soldiers and assassins. On June 1, 2009, months after Max's escape, terrorists detonate an electromagnetic pulse weapon in the atmosphere over the U.S., which destroys the vast majority of computer and communication systems, throwing the country into utter chaos.
The first season begins ten years later in 2019 as it follows the life of the now 19-year-old Max as she struggles to search for her Manticore brothers and sisters. In a United States which is now barely more than a Third World nation (a concept largely dropped from the show after 9/11), she tries to live her life, to evade capture, and to learn to trust and love. She is aided by Logan Cale, an underground cyber-journalist with the alias Eyes Only; Zach, a fellow X-5; and her friends Original Cindy and Sketchy at Jam Pony, a courier company where she works as a bicycle messenger. Other X-5s are periodically introduced as well.
In the second season of the show, the tone changes as Max brings down Manticore and frees the soldiers. She is helped in her escape by Alec, in an attempt to facilitate the assassination and capture of Eyes Only, and Joshua, a transgenic with canine DNA. She later learns that Joshua was the first transgenic created by Manticore's founder Sandeman. Max also finds out that Manticore produced soldiers for speciality environments such as desert and Arctic conditions and consequently look vastly different from normal humans. A major theme in the second season is the discovery of an even more deadly enemy in a millennia-old breeding cult similar in structure to the Illuminati. This has resulted in humans even more formidable than the Manticore-produced transgenics, and even some with strong telekinetic powers. Ames White, a government agent introduced early in the second season trying to eliminate the loose transgenics, is revealed to be a member of the cult. When a strange message written in Max's genetic code makes an appearance on her skin, it is revealed that Sandeman was a renegade from the breeding cult. Ames White is Sandeman's son, which essentially makes him "related" to Max and her transgenic brethren. However, the series was cancelled before the producers could play with this dynamic.