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Multiple primary malignancies have been reported in anecdotal case reports and series in literature. The de novo occurrence poses diagnostic and therapeutic challenges. The co-occurrence of lung adenocarcinoma with acute myeloid leukemia synchronously has been reported in one small series in literature. There is limited data available regarding the treatment and response outcomes in such cases, where both malignancies are molecularly and therapeutically distinct. Hence, a comprehensive workup including a complete molecular profiling is necessary to render appropriate therapy to the patient. This report elucidates the same in a case of concurrent de novo lung adenocarcinoma and acute myeloid leukemia, where complete molecular workup culminated in a successful treatment outcome.