The treatment of malignant pleural mesothelioma continues to pose a significant challenge for clinicians. This review aims to present the latest advancements in the treatment of unresectable malignant pleural mesothelioma, while also considering the details of medication types and dosages in conjunction with tumor histology subtypes. A series of exogenous risk factors directly correlated with the appearance of malignant mesothelioma are reviewed, along with the histological subtypes and the staging system. The systemic treatment during the first line of therapy, subsequent lines of treatment, current immunotherapy options, and health technologies in clinical trials are described in detail. It has been found that for patients with advanced malignant pleural mesothelioma who are not candidates for resection, the initial treatment approach depends on the tumor histology. For those with nonepithelioid histology, first-line treatment with nivolumab and ipilimumab is considered. For patients with the epithelioid histology type, combined chemotherapy with pemetrexed and a platinum agent, with or without bevacizumab, is indicated instead of nivolumab and ipilimumab. However, nivolumab and ipilimumab represent a reasonable alternative, particularly for patients likely to tolerate the chemotherapy regimen poorly.
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