Abstract Background The emergence of immune checkpoint inhibitors (ICI) has changed the landscape of cancer treatment; however, they can cause a variety of side effects. One serious complication is Triple M syndrome, which is a triad of ICI toxicities including myositis, myocarditis, and myasthenia gravis. Little literature regarding pathophysiology and guideline directed treatment exists, but case reports estimate a significant mortality rate of 60%. ICIs that have been recognized are pembrolizumab, nivolumab, and avelumab and ICI use in combination increases the risk of the syndrome. Current treatment regimens consist of steroids, immune modulators, and pyridostigmine. Ultimately, the syndrome requires rapid recognition and treatment to reduce mortality outcomes. Patient Case A 62 y.o. male with metastatic hepatocellular on atezolizumab/bevacizumab presented with a couple day history of progressive proximal upper and lower extremity weakness, mild dysarthria and dysphonia and shortness of breath. His head imaging was negative for acute stroke, but work-up revealed an AST of 1600, ALT of 500, total bilirubin of 9.1 and a CK of 9000. Troponin was also elevated at 273. There was immediate concern for Triple M syndrome given clinical and laboratory evidence of myositis and myocarditis. Therefore, the patient was transferred to the ICU and started on high-dose steroids. Myositis was confirmed via EMG and MRI of the left thigh showing intramuscular inflammation. EMG didn't show evidence of neuromuscular junction abnormalities and myasthenia antibodies were negative. Regarding myocarditis, with troponin elevation, TTE showed a hyperdynamic left ventricle and cardiac MRI displayed focal enhancement of the inferior septum consistent with mild myocarditis. Given worsening liver function and clinical status, IVIG was initiated. Unfortunately, the patient continued to decline and ultimately passed away after transitioning to comfort care.Discussion While this case did not clearly present a diagnosis of Triple M syndrome, two of the three triad were present, and the patient also had evidence of hepatitis, which has been seen with the syndrome. As seen in this case, there is a significant mortality rate, which emphasizes the importance to increase the awareness of Triple M syndrome in patients on ICIs. It also highlights our gap in knowledge regarding pathophysiology, standard diagnostic criteria and targeted treatments. Further research to understand which diagnostic markers are most sensitive and specific would help with early recognition but also inform treatment options. Mortality in Triple M remains high but with further understanding we may be able to counter this severe ICI toxicity.