Purpose of Review <p>Pleural mesothelioma (PM) is a rare yet highly aggressive cancer. It is typically diagnosed at an advanced stage, leaving patients with limited curative options. In this review, we highlight emerging frameworks for patient stratification and summarize advances in conventional therapy, targeted therapy and immunotherapy for PM, and provide some feasible considerations in this challenging field.</p> Recent Findings <p>Recently, targeted therapies, including biomarker-driven therapies and gene-modulating strategies, have shown early clinical activity in molecularly defined patient subgroups. By contrast, immune checkpoint-based approaches have begun to reshape the treatment landscape, demonstrating survival benefit across histologic subtypes and progressing toward frontline use, whereas cancer vaccines, cellular therapies, and oncolytic viruses remain in early stages of clinical development with limited clinical impact to date. In parallel, advances in drug delivery systems such as intrapleural administration, gene delivery platforms, and nanosystems are being explored to improve pleural targeting and potentially mitigate resistance and systemic toxicity.</p> Summary <p>The therapeutic paradigm for PM is shifting toward precision and multimodal treatment. However, many emerging approaches require further validation before broad clinical adoption. With collaborative clinical efforts and translational innovation, more effective treatment strategies may be realized for PM patients.</p>