Abstract: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive malignancy. Due to its insidious onset, most patients are diagnosed at an advanced stage. The primary risk factor for MPM is asbestos exposure, with amphibole and crocidolite asbestos carrying the highest pathogenic potential. According to the 2021 World Health Organization (WHO) classification, MPM is divided into three major histological subtypes: epithelioid, sarcomatoid, and biphasic (mixed). The epithelioid subtype is the most common and associated with relatively better prognosis, while the sarcomatoid subtype has the poorest outcome. Over the past two decades, chemotherapy has remained the standard treatment for MPM, but its efficacy has been limited. In recent years, with the rise of immunotherapy, the combination of nivolumab and ipilimumab demonstrated significant survival benefits in the CheckMate 743 trial, becoming the new standard first-line treatment for unresectable MPM. In 2025, MPM clinical research made key progress in determining optimal first-line regimens for different patient populations, breaking through bottlenecks in second-line and later-line therapies, exploring novel perioperative treatment models, developing new targeted therapies, and investigating new biomarkers. These findings signify that MPM treatment strategies have formally transitioned from the traditional “one-size-fits-all” approach to a new era of precision and stratified treatment based on histological subtypes and biomarkers.