Nuclear carcinoma of the testis (NUT) midline carcinoma are rare, poorly differentiated tumors resulting from t(15; 19) rearrangement, clinically characterized by aggressive and rapid progression to death. No optimal treatment regimen has been established for this rare malignancy. Surgery, chemotherapy, and radiation have been used for treatment alone or in combination, depending on location and staging of the disease, and may confer short periods of remission; however, re-emergence of the disease inevitably occurs. Targeted therapies such as bromodomain and extra-terminal domain protein (BET) inhibitors are currently in early phases of clinical trials. Here we describe a 49-year-old-male with no comorbidities who presented with acute worsening of chronic cough, new onset hemoptysis and left sided chest pain for 2 weeks. Workup revealed stage IIIB NUT midline carcinoma (NMC) of the lung with next-generation sequencing confirming the presence of a NUTM1-BRD4 fusion. The tumor was unresectable, and he began concurrent chemoradiation with weekly carboplatin and paclitaxel for 5 weeks. The follow-up CT scan showed partial response, so maintenance was continued with durvalumab. Two months later, he presented with metastasis to the posterior muscle compartment of the left arm, which was treated with local radiotherapy. Four months later he developed progression of lung disease with multiple pulmonary nodules. Durvalumab was discontinued and he was prescribed the BET inhibitor molibresib, 120 mg daily. After nearly 3 months of treatment with molibresib, he presented with brain metastasis for which he had a craniotomy with tumor resection and gamma knife radiation to solitary metastatic lesions. He was then prescribed chemo-immunotherapy with carboplatin plus pemetrexed and pembrolizumab. After two cycles of treatment his disease progressed, and he succumbed to it. Total survival was 18 months. In conclusion, NUT midline lung carcinoma is a rare but aggressive malignancy and patients have limited treatment options especially in advanced stages. Few targeted therapies have shown promising results in early clinical trials but more treatment options are awaited.