Patients with pancreatic cancer (PCa) have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic. Yet, it suffers from certain limitations during clinical exploitation, including insufficient photosensitiz-ers (PSs) delivery, tumor-oxygenation dependency, and treat-ment escape of aggressive tumors. To overcome these obstacles, an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles (NPs) by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribu-tion of photosensitizers. Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation. A num-ber of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment. This review provides an overview of available data regarding the design, meth-odology, and oncological outcome of the innovative NPs-based PDT of PCa.