Precision medicine approaches using ex-vivo drug sensitivity testing (DST) have received attention in the cancer research community as a means to improve treatment stratification in populations where multiple treatment attempts are not feasible, or no standard-of-care treatment exists, such as ultra-rare cancers with a significant clinical need for effective treatment options, like osteosarcoma. DST has the potential to supplement existing patient stratification approaches by providing tumor-specific response data to aid in treatment selection at the time of treatment decision. We present the case of a pediatric osteosarcoma patient who was evaluated using DST at the time of standard-of-care treatment to evaluate treatment sensitivity. The DST screen indicated significant treatment sensitivity to anthracyclines and methotrexate, consistent with the first-line standard-of-care therapy (MAP). Clinical follow-up showed treatment sensitivity to standard-of-care MAP treatment and pathology results of 90% necrosis. The present case shows that DST screening is feasible from a technical standpoint, can be performed in a clinically relevant time frame that does not delay treatment start, and provides personalized drug sensitivity information on clinically available agents, and the DST results align with the clinical treatment response.