Chemiluminescence substances that respond to hydrogen peroxide (H₂O₂) in a tumor microenvironment have the potential to achieve accurate tumor imaging. Here, Pluronic F-127 (PF127) and polymers containing oxalate ester (POE) were assembled by hydrophilic and hydrophobic forces to form nanoparticles to load the anti-tumor drug lapachone (Lapa) and rubrene. The Lapa-loaded H₂O₂-responsive nanoparticles (L-HPOX) could track tumors in vivo through H₂O₂-related chemiluminescence. With the presence of H₂O₂ in the tumor microenvironment, L-HPOX would collapse and release the loaded drug for anti-tumor therapy. After treatment with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), the inflammatory level and H₂O₂ content increased. Thus, L-HPOX exhibited good capabilities of tumor imaging and treatment. Importantly, the immune system was also activated for anti-metastatic activity. This intelligent and efficient chemiluminescent tumor theranostic nanoplatform will find great potential for precise and efficient tumor treatment.