Conventional cancer therapies, such as chemotherapy and phototherapy, often face limited efficacy and severe side effects. Nanocarrier-based combination strategies offer a promising alternative. Here, we developed a multifunctional hollow porous Prussian blue (HPB)-based nanoplatform, designated DRHP, co-loaded with doxorubicin (DOX) and Radachlorin (RADA) for synergistic chemo-photothermal-photodynamic therapy. HPB nanoparticles were obtained by acid etching of solid PBNPs, followed by drug encapsulation and poly(acrylic acid) coating for stability. The nanoplatform exhibited uniform but polyhedral morphology with nanoscale dimensions, high drug loading, and pH-responsive release. RADA showed a faster release than DOX under acidic conditions. DRHP demonstrated strong and stable photothermal conversion under both 808 and 660 nm laser irradiation. In vitro assays using B16F10 melanoma cells confirmed that DRHP induced marked cytotoxicity under dual-laser treatment, showing synergistic efficacy compared with single-modality nanoparticle systems. In summary, DRHP integrates chemotherapy, photothermal therapy, and photodynamic therapy in a single nanoplatform, enhancing in vitro anticancer activity and laying the groundwork for further in vivo evaluation.