A three-in-one self-assembled metallo-nanophotosensitizer system (NLCD) was constructed by cooperative coordination of amphiphilic L-arginine-modified photosensitizer NBS-L-Arg and DOX in the presence of Cu²⁺via the synergy of coordination, hydrophobic, and π–π stacking interactions. The resulting NLCD NPs possessed uniform size, well-defined nanosphere structure, and GSH-responsive ability. In vitro studies exhibited that NLCD NPs integrating photodynamic/chemodynamic/chemo multimodal therapy achieved an enhanced therapeutic effect.