On her 50th birthday, faded Hollywood star Elisabeth Sparkle is dismissed from her TV show and discovers a black-market serum, “The Substance,” that can generate a younger version of herself. As she and her new alter ego, Sue, switch bodies weekly, their relationship deteriorates, leading to jealousy, betrayal, and horrific consequences. When Sue’s reckless disregard for the switching schedule causes both women to deteriorate, a grotesque mutation emerges, culminating in a deadly, chaotic live broadcast. Elisabeth’s original face, now a decaying relic, ultimately melts into oblivion, symbolizing the price of vanity and fame.