Toxic was filmed on a soundstage in Los Angeles, California and begins with an open shot of an airplane flying surrounded by many doves. Spears appears with blond hair dressed as a flight attendant, receiving a phone call. After serving some of the passengers, she leads a bald overweight man to the bathroom and seduces him. She takes off the man's mask to reveal an attractive man (Matthew Felker) and steals a black pass from his pocket. Spears is then dropped into the back of a Ducati 999, driven by a shirtless male (Tyson Beckford) in a futuristic Paris, that was compared to the 1982 film Blade Runner. She wears a tight black catsuit and sports red hair, inspired by the character of Sydney Bristow from television series Alias. They pass a woman and lift up her dress, a homage to the iconic Marilyn Monroe scene in the 1955 film The Seven Year Itch. They also pass two women frolicking in a store window.
Throughout the video, there are scenes of Spears naked covered in diamonds. Spears then enters Toxic Industries, and gains access to a vault from which she steals a vial of green poison. She accidentally triggers a laser trap when she leaves that she evades with elaborate dance moves, including a back handspring. This is followed by scenes of Spears wearing a black superheroine outfit and black hair. She scales a building and enters an apartment, where her unfaithful boyfriend (Martin Henderson) is waiting. She kisses him just before pouring the poison into his mouth, killing him. Spears kisses him again and jumps out of the window. She lands back on the plane sporting her flight attendant outfit, and winks at the camera. The video closes with a shot of the airplane flying surrounded by doves like the beginning.