Placental Site Trophoblastic Tumor (PSTT) is a rare malignancy that often presents with extensive disease and can be resistant to traditional treatments. We present the case of a woman with stage IV PSTT who was initially managed with neoadjuvant chemotherapy followed by tumor debulking. Adjuvant therapy was guided by further pathologic analysis that revealed high levels of staining for PD-L1 as well as the presence of tumor infiltrating lymphocytes (TILs). Subsequently, the patient was treated with traditional chemotherapy with the EP/EMA regimen with the addition of pembrolizumab. The patient’s treatment course was complicated by the development of pulmonary arteriovenous malformations, autoimmune thyroiditis thought to be secondary to immunotherapy, and significant tinnitus secondary to platinum agents. Currently the patient is in follow up and remains in a complete remission.