Hollow mesoporous structures with interior cavities and expanded surface area have attracted considerable interest as drug delivery systems. In this study, a multifunctional nanotheranostic agent was developed by conjugating indocyanine green (ICG) and loading doxorubicin (DOX) onto the surfaces or within the cavities of hollow mesoporous Prussian blue (HMPB) nanoparticles, known as HMPB@PEI/ICG/DOX or simply HPID NPs, which were investigated as phototheranostic agents for in vivo fluorescence imaging and light-induced chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT). These original HPID NPs exhibited strong near infrared (NIR) absorbance, reactive oxygen species (ROS) yield, and controlled chemotherapeutic drug release behavior. After intravenous injection of HPID NPs, highly efficient solid tumor ablation effects were observed in 4T1 tumor-bearing mouse models under NIR laser irradiation. Additionally, there was insignificant low-term toxicity or damage to normal tissues, as evidenced by histopathological and hemocompatibility analyses, suggesting that this agent has reliable biosafety for systemic applications. Taken together, the results of this study suggest that HPID NPs can produce tumor-specific and stimuli-triggered theranostic effects under tri-modal combination therapy. These HPID NPs advantageously provide traceable accumulation and activation and therefore could be a capable mediator in nanomedicines for eliminating solid tumors.