Triple M Overlap Syndrome (TMOS) is a rare and severe complication of immune checkpoint inhibitor (ICI) therapy, characterized by concurrent myocarditis, myositis and myasthenia gravis. There is a scarcity of evidence regarding this syndrome, underscoring the need for further research and reporting. We report the case of a woman in her 70s with stage IV microsatellite instability-high (MSI-H) colon cancer who developed generalized myalgias and muscle weakness, along with bulbar and ocular symptoms, two weeks after the first administration of pembrolizumab. Laboratory tests revealed elevated creatine kinase, transaminase and troponin levels. Cardiac magnetic resonance imaging (MRI) findings were suggestive of myocarditis. Due to the constellation of myocarditis, myositis and myasthenia gravis, TMOS was diagnosed. Despite initial improvement with corticosteroid pulses, the patient's clinical condition deteriorated, culminating in the need for mechanical ventilation due to respiratory failure. Sequential treatment with intravenous immunoglobulin (IVIG) and, ultimately, plasmapheresis resulted in gradual clinical improvement. After a prolonged Intensive Care Unit (ICU) stay, she was admitted to the medical ward, where she continued to improve with speech therapy and motor rehabilitation. ICI therapy was permanently discontinued. A high level of suspicion is necessary for the diagnosis of this rare syndrome, and multidisciplinary collaboration is critical to optimize clinical outcomes. This case highlights the importance of evaluating myocarditis, myositis and myasthenia when any of them is diagnosed in a patient receiving ICIs. Prompt treatment initiation and ICI therapy discontinuation are crucial to maximizing the chances of a positive outcome.