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Photodynamic therapy (PDT) has shown promise as an adjuvant treatment for malignant pleural mesothelioma when combined with surgical resection. Accurate light dosimetry is critical for treatment efficacy. This study presents an improved method for analyzing light fluence distribution in pleural PDT using a standardized anatomical coordinate system and advanced computational modeling. We utilized an infrared navigation system with an improved treatment delivery wand to track light delivery in real-time. The human chest cavity geometry was reconstructed and the pleura was mapped to a standardized coordinate system, allowing for direct comparisons across patients. Light fluence was calculated using both primary and scattered components, with a novel dual correction method applied to match measured values at detector locations. The standardized approach allowed for statistical analysis of light fluence distribution across anatomical regions in a cohort of 11 patients. Results showed acceptable light fluence uniformity with a standard deviation of 6.6% from the prescribed dose across patients. This comprehensive analysis provides insights for optimizing treatment protocols and lays the groundwork for future studies on singlet oxygen generation and its correlation with treatment outcomes in pleural PDT., (© 2025 American Society for Photobiology.)