B7-H3 is a member of the B7 family of immune checkpoint (IC) proteins that plays a critical role in cancer immunotherapy. It exerts both co-stimulatory and co-inhibitory effects on immune cells, contributing to tumor progression and resistance to immunotherapy. B7-H3 is aberrantly expressed in various solid malignancies, including hepatocellular carcinoma (HCC), pancreatic adenocarcinoma (PAC), gastric cancer (GC), breast cancer (BC), and renal cell carcinoma (RCC), and is associated with advanced disease, poor prognosis, and resistance to treatment. Anti-B7-H3 agents, including monoclonal antibodies (mAbs), bispecific antibodies, antibody-drug conjugates (ADCs), CAR-T cells, and radioimmunotherapy, have shown promising preclinical activity and are currently being evaluated in clinical trials. B7-H3 expression is localized in the cytoplasm, cell membrane, and nucleus, with distinct patterns in different cancers. Its soluble form (sB7-H3) is also present and may influence the efficacy of anti-B7-H3 therapies. B7-H3 interacts with various receptors, including TLT-2, IL-20Rα, and PLA2R1, and contributes to immune suppression, tumor growth, and metastasis. B7-H3 is involved in multiple signaling pathways that promote tumor cell survival, proliferation, and resistance to therapy. In clinical settings, B7-H3 is a promising target for immunotherapy, with several agents in development for various cancers. The role of B7-H3 in cancer immunotherapy is an emerging area of research, with potential to improve treatment outcomes for patients with solid malignancies.B7-H3 is a member of the B7 family of immune checkpoint (IC) proteins that plays a critical role in cancer immunotherapy. It exerts both co-stimulatory and co-inhibitory effects on immune cells, contributing to tumor progression and resistance to immunotherapy. B7-H3 is aberrantly expressed in various solid malignancies, including hepatocellular carcinoma (HCC), pancreatic adenocarcinoma (PAC), gastric cancer (GC), breast cancer (BC), and renal cell carcinoma (RCC), and is associated with advanced disease, poor prognosis, and resistance to treatment. Anti-B7-H3 agents, including monoclonal antibodies (mAbs), bispecific antibodies, antibody-drug conjugates (ADCs), CAR-T cells, and radioimmunotherapy, have shown promising preclinical activity and are currently being evaluated in clinical trials. B7-H3 expression is localized in the cytoplasm, cell membrane, and nucleus, with distinct patterns in different cancers. Its soluble form (sB7-H3) is also present and may influence the efficacy of anti-B7-H3 therapies. B7-H3 interacts with various receptors, including TLT-2, IL-20Rα, and PLA2R1, and contributes to immune suppression, tumor growth, and metastasis. B7-H3 is involved in multiple signaling pathways that promote tumor cell survival, proliferation, and resistance to therapy. In clinical settings, B7-H3 is a promising target for immunotherapy, with several agents in development for various cancers. The role of B7-H3 in cancer immunotherapy is an emerging area of research, with potential to improve treatment outcomes for patients with solid malignancies.