Plot

A fading celebrity takes a black-market drug: a cell-replicating substance that temporarily creates a younger, better version of herself.

Have you ever dreamt of a better version of yourself? You. Only better in every way. Seriously. You've got to try this new product. It's called The Substance. It changed my life. It generates another you. A new, younger, more beautiful, more perfect, you. And there's only one rule: You share time. One week for you. One week for the new you. Seven days each. A perfect balance. Easy. Right? If you respect the balance... what could possibly go wrong?—Festival Cannes

On the day that the actress Elisabeth Sparkle is fifty years old, her former successful career downfalls and the producer Harvey call her show off, telling her that he needs a new face on TV. The upset Elisabeth drives home and is distracted by the removal of the billboard of her TV show and is hit by a truck. She wakes up in the hospital and the male nurse gives a flash drive to her with the title "The Substance". When she arrives home, she watches the video about a substance that would split her in two, with a more perfect and beautiful younger version of her. But there is a rule, their time will be shared, and they will not coexist. One week Elisabeth lives, the other week her new version lives without exception. In principle reluctant, Elisabeth decides to use the substance. She generates a gorgeous woman that goes to the audition to be the substitute for Elisabeth's show. When they ask her name, she says Sue and is immediately hired by Harvey. Elisabeth and Sue live seven days each in principle taking care of the dormant one, feeding each other in accordance with the rules. But although being just one, the washed-up Elisabeth feels jealous of Sue's success while her younger version wants to live more than seven days to enjoy life. Soon their feelings bring tragic consequences.—Claudio Carvalho, Rio de Janeiro, Brazil

Elisabeth Sparkle, a fallen Hollywood idol pushing 50, sees her glittering world unravel after an agonising meeting with her TV producer. And just like that, years of contribution to the cut-throat entertainment industry went down the drain. Now, Elisabeth would do anything for another shot. Fortunately, she won't have to sell her soul to stay in the game; Elisabeth only needs to try The Substance. After all, she has nothing to lose--if Elisabeth plays her cards right, the miraculous solution will deliver on its wild promise. However, with so much at stake, there is always a temptation to cut corners when time is short. As an empowered new version of the once-beloved star emerges, so does a haunting question: How long can a beautiful lie deceive the world?—Nick Riganas

On her 50th birthday, Elisabeth Sparkle, a once-celebrated but now-faded Hollywood movie star, is abruptly dismissed from her long-running aerobics TV show by the producer, Harvey, due to her age. Distraught, Elisabeth crashes her car while distracted by a billboard of herself being taken down. At the hospital, a young nurse covertly gives her a flash drive advertising "The Substance", a black market serum that promises a "younger, more beautiful, more perfect" version of oneself.

Elisabeth, intrigued and desperate, orders The Substance and injects the single-use activator serum. She convulses as her body generates a younger version of herself, Sue, who splits out from a slit in her back. The two bodies must switch consciousness every seven days without exception, with the inactive body remaining unconscious and fed intravenously with a weekly food supply. Daily injections of stabilizer fluid, extracted from the original body, are necessary to prevent Sue from deteriorating.

Sue quickly becomes an overnight sensation as Elisabeth's replacement on the TV show, leading a hedonistic lifestyle and enjoying her newfound fame and is offered the chance to host the prestigious New Year's Eve Show. Elisabeth, meanwhile, becomes a self-hating recluse. Nearing the end of her allotted weekly cycle, Sue parties and brings a man home for casual sex, delaying the switch and causing Elisabeth's right index finger to age rapidly. Elisabeth contacts the supplier, who warns her about the consequences of staying in the other body too long. Despite their shared consciousness, Elisabeth and Sue begin to view themselves as separate individuals and grow to despise each other; Elisabeth resents Sue for her frequent disregard of the switching schedule, which further exacerbates her aging, while Sue is disgusted by Elisabeth's constant self-loathing. Following a particularly destructive episode as Elisabeth, Sue stockpiles stabilizer fluid and refuses to switch back.

Three months later, the day before the New Year's Eve telecast, Sue runs out of stabilizer fluid. Desperate, Sue contacts the supplier, who informs her that she must switch back to replenish the supply. When they finally switch, Elisabeth finds herself horrifically transformed into a deformed and near-hairless hunchback. Determined to stop Sue, Elisabeth acquires a serum designed to terminate her. However, still craving admiration, Elisabeth stops before fully injecting the serum and resuscitates Sue, leaving both of them conscious. Realizing Elisabeth's intent upon seeing the near-empty syringe, Sue attacks and kills her before leaving to host the New Year's special.

Without Elisabeth, Sue's body begins to deteriorate. In a panic, she attempts to create a new version of herself using leftover activator serum, despite warnings from the supplier. This results in the creation of a grotesque mutated body, "Monstro Elisasue", with both Sue and Elisabeth's faces. Monstro Elisasue, dressed up in a mask cut from a poster of Elisabeth, limps onto the stage during the live broadcast. The mask falls off, causing the horrified audience to erupt into chaos and attack her. A man decapitates her, only for an even more mutated head to grow back. Her arm holding the mic-stand snaps off, drenching the audience in blood. Elisasue flees the studio but collapses into viscera. Elisabeth's original face detaches from the gore, crawling onto her neglected star on the Hollywood Walk of Fame. She smiles as she hallucinates being admired by everyone before melting into a puddle of pulp. The next day, her blood is cleaned up by a floor scrubber.