The Lübeck Disaster of 1930, a public health tragedy resulting from the inadvertent administration of contaminated Bacillus Calmette-Guérin (BCG) vaccines to neonates in Lübeck, Germany, had profound implications for both tuberculosis (TB) control and modern therapeutic applications of BCG. While the incident caused significant morbidity and mortality, leading to ethical and procedural overhauls in vaccine development, its scientific legacy persists in the field of immunotherapy. The unique immunomodulatory properties of BCG, originally developed as a TB vaccine, were first illuminated during early investigations into the disaster. Decades later, this understanding catalyzed its application in bladder cancer treatment. BCG’s ability to elicit a robust localized immune response became the foundation for its role in intravesical therapy for non-muscle-invasive bladder cancer, where it remains a first-line treatment. This paper explores the historical context of the Lübeck Disaster, the insights it provided into the immunological mechanisms of BCG, and how these findings have informed its safe and effective use in oncology. By tracing the trajectory from public health catastrophe to therapeutic innovation, the Lübeck Disaster underscores the importance of rigorous vaccine protocols and exemplifies how medical missteps can yield transformative scientific advancements.