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An 85-year-old man with recently diagnosed metastatic EGFR+ lung adenocarcinoma treated with osimertinib presented after 1 month of therapy in decompensated congestive heart failure along with atrial fibrillation, prolonged QTc and acute kidney injury. Osimertinib was held. His hemodynamic status was optimized, and he was started on cardioprotective medications (losartan and metoprolol succinate), and LVEF recovered. However, after reintroducing osimertinib, LVEF reduced, indicating possible osimertinib-induced cardiomyopathy. An SGLT2 inhibitor was added for cardioprotection before another rechallenge of osimertinib. SGLT2 inhibitors are a powerful tool for heart failure and may have a potential secondary benefit in ameliorating cardiotoxic processes. Although their use in osimertinib-induced cardiomyopathy has not been well-established, current heart failure guidelines and emerging research support its use in this setting. This case and the accompanying literature review highlight the novel use of SGLT2 inhibitors coupled with regular clinical and imaging monitoring, as a compelling intervention for osimertinib-induced cardiomyopathy., Competing Interests: Dr Clasen is supported in part by National Institutes of Health-NCI Grant 2L30CA264679-02; has performed a personal consulting or advisory role for Sumitomo Pharma Oncology; and has family member employment and stock/other ownership interests in Eli Lilly and Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.)