The development of targeted nanotherapeutics that enhance tumor specificity while minimizing systemic toxicity remains a central challenge in bladder cancer treatment. Herein, we engineered a biomimetic nanoplatform (mPPE@DOX) by cloaking a poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG--PCL) core, co-loaded with doxorubicin (DOX) and vitamin E, with a membrane derived from MB49 bladder cancer cells. This design leverages homologous targeting for improved tumor accumulation and combines the chemotherapeutic action of DOX with the chemosensitizing function of vitamin E. The resulting nanoparticles demonstrated excellent colloidal stability, high drug-encapsulation efficiency, and efficient cellular internalization, leading to enhanced lysosomal escape, pronounced DNA damage, and synergistic apoptosis induction in vitro. In an orthotopic MB49 bladder cancer model, mPPE@DOX exhibited prolonged blood circulation, superior tumor-targeted delivery, and potent inhibition of tumor growth, which translated into a significant survival benefit. Importantly, this robust antitumor efficacy was achieved with markedly reduced systemic toxicity compared to free DOX. These findings highlighted a promising biomimetic strategy for precise and effective combination therapy against bladder cancer.