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Cancer therapeutics-related cardiac dysfunction is currently of great concern as one of the pivotal therapeutic targets of onco-cardiology. Only a few studies have reported the occurrence of heart failure following the administration of osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor for EGFR mutation-positive advanced non-small cell lung cancer. We report on a 74-year-old woman with osimertinib-induced advanced heart failure with reduced ejection fraction, which was treated by the temporal termination of osimertinib and neurohormonal blocker therapy, as well as heart rate modulation therapy using ivabradine. Despite osimertinib-induced heart failure being relatively rare, aggressive neurohormonal blocker therapy using ivabradine if applicable, as well as the temporal termination of osimertinib, might be a promising therapeutic strategy.