Based on true events, "Lady of Guadalupe" is a moving religious discovery juxtaposing folklore and the present day. Historically significant recreations are used to illustrate the origin of her prevalent and powerful symbolism of Mexican identity and faith. When a young and ambitious reporter (Guillermo Iván) is assigned an article on faith, he finds himself enmeshed in the legend of Juan Diego and Our Lady of Guadalupe. Skeptical of miracles and the importance of modern-day Christianity, the reporter's investigation takes him from cynic to true believer as his personal limits are tested.

Things take a turn for the worst when a group of bickering filmmakers join a suspicious film festival on the site of a mysterious murder.