Purpose of Review <p>This review explores the emerging role of patient-derived organoids (PDOs) in advancing precision medicine for malignant pleural mesothelioma (PM), focusing on their development, characterization, and translational potential.</p> Recent Findings <p>Recent studies have successfully established PM PDOs from pleural effusions and biopsy samples, showing high fidelity to parent tumours in morphology and genetics. These models have enabled assessment of chemotherapy and immunotherapy responses and identification of biomarkers linked to tumour heterogeneity and the tumour microenvironment.</p> Summary <p>PM-derived organoids represent a promising preclinical platform for therapeutic stratification, biomarker discovery, and drug screening. By better reflecting tumour biology, PDOs may accelerate individualized treatment development and improve clinical outcomes for PM patients.</p>