Malignant mesothelioma is an aggressive cancer with a poor prognosis and limited treatment options. For many years, the only US Food and Drug Administration‐approved first‐line treatment for unresectable mesothelioma was pemetrexed plus cisplatin. However, the recent approval of nivolumab plus ipilimumab as frontline treatment for patients with pleural mesothelioma marks a significant milestone for the treatment of this disease. In this review, the authors describe recent advances in therapeutic strategies for the treatment of patients with advanced, unresectable mesothelioma, highlighting the emerging use of immunotherapy and mesothelin‐targeted therapies for the management of malignant mesothelioma. The emerging use of immunotherapy and mesothelin‐targeted therapies for the management of malignant mesothelioma is reviewed. The future outlook for patients with mesothelioma is promising, and progress in the treatment of advanced mesothelioma offers patients more options beyond standard chemotherapy and opportunities to achieve better outcomes.