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Malignant peritoneal mesothelioma, a neoplastic process that arises from the peritoneal membranes and presents as a diffuse malignant process, has an incidence of approximately 400-600 new cases annually in the United States. Systemic chemotherapy regimens, like the combination of cisplatin and pemetrexed, have response rates of approximately 25% in peritoneal mesothelioma. Due to chemotherapy’s poor response rates, the first line approach to treating malignant peritoneal mesothelioma over the last 30 years has been surgical resection with regional intra-peritoneal chemotherapy in appropriately selected patients. Hyperthermic intraoperative intraperitoneal perfusion with chemotherapy with cisplatin or mitomycin c for 90 to 120 minutes is the most commonly reported type of regional chemotherapy that is administered during surgical cytoreduction. Favorable prognostic factors for patient outcomes after cytoreduction and hyperthermic intraperitoneal perfusion with chemotherapy tend to be favorable operative characteristics (lower peritoneal cancer index, better complete cytoreduction score), less aggressive tumor characteristics (epithelioid histology, low Ki-67, well-differentiated), and other patient characteristics (young, female, fewer comorbidities). Recently, there has been considerable interest in the utility of immune checkpoint inhibitors either alone or in combination with chemotherapy for patients with mesothelioma. Data demonstrate that programmed death-ligand 1 may be highly expressed in a large proportion of malignant peritoneal mesothelioma tumors and therefore the evaluation of checkpoint blockade in this patient population is a high clinical priority.