A tumor cell membrane (CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy. However, a single CM mostly has a weak immune-boosting effect. Here, a heterogenic fusion membrane tumor vaccine, EV-CM, was successfully constructed by fusing extracellular vesicles (EVs) from S. aureus and CM from B16F10 melanoma cells. Inheriting the advantages of parental components, the EV-CM combines tumor antigens with natural adjuvants that can be used for immunotherapy and can be easily synergistic with complementary therapies. In vivo vaccine tests have shown that EV-CM can activate immune antitumor responses and prevent tumorigenesis. To further enhance the immunotherapeutic and antimetastatic effects of EV-CM, Pt-porphyrin coordination polymer as an immunopotentiator (CPIP) was implanted into an EV-CM nanoplatform (CPIP@EV-CM), which combines localized sonodynamic/chemodynamic therapy-induced immunogenic cell death with heterogenic fusion membrane-mediated antigen-presenting functions. In vitro performance tests, cell experiments, and in vivo animal models have confirmed that the CPIP@EV-CM combined with US has better ROS production, tumor cell killing, and antimetastasis abilities. The heterogenic fusion membrane strategy and ultrasound-augmented nanoplatform present exciting prospects for designing tumor-immunogenic, self-adjuvant, and expandable vaccines, providing new ideas for exploring new melanoma immunotherapy and antimetastasis strategies, which is expected to be used as a safe and effective treatment in clinical practice.