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Cancer remains a serious challenge to public health, with breast cancer, lung, and colorectal cancers predominating in both incidence and deaths worldwide. Significant advances have been made in the therapeutic treatment and resolution of non-solid tumors using immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy to break immune tolerance and initiate tumor clearance. However, these innovative strategies have enjoyed only limited success with solid tumors, especially in late-stage cancers in which tumor size is large. An immunosuppressive tumor microenvironment (TME) that surrounds and protects solid tumors significantly confounds the ability of the host immune system to target and eliminate tumor tissue. Novel technologies using nanomedicines have begun to yield promising results by penetrating into the microenvironment to stimulate innate immunity and induce trafficking of activated antigen presenting cells to regional lymph nodes, ultimately leading to tumor-specific adaptive immune responses. One type of nanomedicine that is generating increasing enthusiasm in the field of immunotherapy are bacterial outer membrane vesicles (OMVs) that can be genetically engineered to surface-express tumor-associated antigens; the resulting recombinant OMVs (rOMVs) can then be purified as immunotherapeutic vaccines. Recent data from experimental animal models have demonstrated remarkable efficacy in tumor challenge models. Such promising experiments suggest the possibility of translating these novel strategies into success with solid tumors in clinical trials. In this review, we will summarize current research using purified rOMVs as immunotherapeutic vaccines and further discuss potential obstacles that still need to be adequately addressed to ensure success in human trials.