Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has emerged as a standard treatment in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. While it is generally well tolerated, milder side effects of diarrhea, cytopenia, and cutaneous rashes are common. Osimertinib-induced myositis and rhabdomyolysis are exceedingly rare, and only a few cases have been documented in the literature to date. In this report, we present a case of a 59-year-old female with metastatic NSCLC who experienced myalgia following the initiation of osimertinib. Blood work revealed elevated creatine kinase (CK), serum creatinine (Cr), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Initially, her myalgia improved, and lab work normalized after drug discontinuation and supportive care. However, rechallenge with a 50% dose resulted in recurrence of symptoms and elevated serum CK, Cr, ALT, and AST. MRI findings suggested diffuse inflammation and a muscle biopsy revealed necrotizing myopathy. Symptoms ameliorated upon complete cessation of the drug and use of steroids. This case highlights the importance of recognizing this rare adverse effect of osimertinib and a guide for managing these associated symptoms.