The cure rate of cancer is increasing with the development of new treatment methods, including surgical treatments and immunotherapy. Nevertheless, treatment of metastatic cancer remains challenging. Immunotherapy is thought to suppress metastatic cancer, as it promotes specific killing of tumor cells via recognition of cancer antigens. This antigen-specific immunity involving helper T cells and cytotoxic T lymphocyte activation is mediated by antigen presentation and stimulation of dendritic cells (DCs). Nonetheless, the strategies aimed at treating metastatic cancer by inducing the activation of DCs have not achieved substantial results. Notably, inducing apoptosis in tumor cells has also been explored as a potential therapeutic strategy. Apoptotic bodies (ABs), which are small membrane-bound vesicles released by dying cells during apoptosis, have been investigated as drug delivery vehicles to specifically target and destroy tumors. However, by inducing transforming growth factor-β and interleukin-10, ABs could inhibit macrophage activation, thereby suppressing immune responses to antigens and promoting immune tolerance. Consequently, the therapeutic application of ABs in tumor immunotherapy remains limited due to their potential to promote immune tolerance. Nonetheless, ABs derived from tumor cells contain abundant tumor antigens. If sufficient immune activity can be elicited, these ABs may serve as a potential therapeutic approach for metastatic cancer. Therefore, we hypothesized that generating ABs using tumors extracted from a bilateral tumor model that mimics metastatic/residual disease and enhancing their immunogenicity could provide an effective strategy for treating metastatic cancer.