Cleo had a rare mutation to the Fox-03 gene, linked to a longer life expectancy.
After attending Lydia Tyrell's birthday party in November 2019, Cleo, Isobel, and their chauffer Arkady went missing. Days later, Cleo and her mother reached the spot where they were to meet Malak. However, Malak was late and two men and a woman attacked the mother and child. Isobel urged Cleo to close her eyes as she quickly incapacitated the group. Malak finally showed up soon after.
Malak led them to an underground community and introduced them to "the Lung." After Cleo's mother disguised them, the Lung prepared them for a venture out of the city, during which they would be escorted by "the Bones."
Former Blade Runner Aahna "Ash" Ashina soon arrived to retrieve Cleo and was informed of Selwyn and Eldon Tyrell's plan to give Cleo over to the Tyrell Corporation as payment for her replicant mother. Selwyn and Tyrell men arrived at El Santuario, prompting a gunfight. With Isobel staying to provide them with cover fire, Cleo was taken by Ash back to Los Angeles, deciding to look after her. Ash then asked Cleo of another safe place, to which Cleo pointed up in the air.
The pair escaped to the Off-world colonies, where by 2026, they lived as mother and child, Cleo disguised as a boy and making a living as a trader known as "the Rabbit." Through her work, she befriended the replicant Padraic, who rescued her from a violent replicant uprising.
On Ramanuja, the group went to an aquarium owner, who gave them information about an eye surgeon who would remove their eyes containing their replicant serial numbers. However, Padraic opted out of the surgery, a move that Cleo criticized. The pair split off from the group and met with Hartawan, requesting help in reaching Arcadia. The Hartawan recommended that they change their appearances before boarding a transport.
A week later, as they prepared to board, they saw Ash, along with Hythe and another replicant of her mother. As Hythe held Ash at gunpoint, Padraic tackled her, but was killed with her sidearm. Cleo went to her mother, who then killed Hythe. Ash then left Cleo in the care of Isobel so that they could reach Arcadia.
Cleo and Isobel delayed their trip, in order to follow Ash back to Earth so they could confront Alexander, admitting that he promised to give Cleo to Eldon Tyrell in order for her to be experimented on, as payment for the first replicant of Cleo's mother. As her father suggested they become a family again, Cleo ran to hug him before making her way to the injured Ash. Isobel went to Alexander, but broke his neck, prompting a Hythe replicant to prepare to kill her, only to be stopped by another defective Hythe.
Cleo, Isobel, and Ash returned to the city and dined at a noodle bar, where Cleo and Isobel confirmed their plans to go to Arcadia, offering to bring Ash along. However, Ash declined, deciding instead to stay, believing it was where she belonged in order to assist Nexus-8s.