This case highlights the fulminant potential of myasthenia-myositis overlap after programmed death-ligand 1 (PD-L1) plus cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade, underscores the importance of early biomarker surveillance and rapid escalation to immunomodulatory therapy, and illustrates the need for early goals-of-care discussions in patients facing severe immune-related toxicities. The gene discussed is CD274; the disease is Fatigable weakness.