Osteosarcoma is the most common primary bone malignancy, and surgical resection combined with neoadjuvant chemotherapy is the gold-standard treatment for affected patients. Although the overall survival rates for patients with osteosarcoma currently range from 60% to 70%, outcomes remain disappointing for patients with recurrent, metastatic, or unresectable disease. Irreversible electroporation (IRE) is a novel ablation technique with the potential to elicit an immune response in solid tumors. Dendritic cell (DC)-based tumor vaccines have shown promising therapeutic efficacy in preclinical studies focused on osteosarcoma; however, only limited therapeutic efficacy has been observed in clinical trials. Thus, there is considerable potential therapeutic value in developing combination osteosarcoma treatments that involve IRE and DC-based tumor vaccines. In this review, we discuss recent advances in preclinical and clinical DC-based immunotherapies, as well as potential combinations of DC-based vaccines and IRE, that may improve therapeutic outcomes for patients with osteosarcoma.