The Disappearance of Irene Dos Santos is an elaborate story of two childhood friends, Lily and Irene. Despite their differences, Lily Martinez, who comes from a middle class family, and Irene Dos Santos, who comes from a wealthier family, quickly become friends while attending a private school together in Caracas, Venezuela.
Irene is "the controller in their society of two." She introduces Lily to her first boyfriend and teaches her how to French kiss.