Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of nonsmall-cell lung cancer (NSCLC). It carries a poor prognosis, even among other subtypes of NSCLC. Currently, most treatment strategies for PSC are derived from regimens aimed at managing soft tissue sarcomas or NSCLC. The use of doxorubicin plus ifosfamide and pemetrexed has been well established in the management of soft tissue carcinoma and other nonsmall-cell lung cancers, respectively. We report the case of a 69-year-old male diagnosed with PSC who was managed with doxorubicin plus ifosfamide and pemetrexed therapy. Our patient initially responded to the therapy but had rapid progression and died 8 months after the initiation of treatment. Upon genetic analysis, it was revealed the patient had overexpression of the MDM2 protein, which has been associated with poor response to therapy. This case highlights the need for a personalized treatment approach, as well as the need for a standardized treatment regimen for managing PSC.