Patients with extracranial tumors, like lung, breast, and skin cancers, often develop brain metastases (BM) during the course of their diseases and BM commonly represent the terminal stage of cancer progression. Recent insights in the immune biology of BM and the increasing focus of immunotherapy as a therapeutic option for cancer has prompted testing of promising biological immunotherapies, including immune cell-targeting, virotherapy, vaccines, and different cell-based therapies. Here, we review the pathobiology of BM progression and evaluate the potential of next-generation immunotherapies for BM tumors. We also provide future perspectives on the development and implementation of such therapies for brain metastatic cancer patients.