Transmembrane emp24 protein transport domain containing 3 (TMED3) is a member of the P24 protein family, which has become a biological research hotspot in recent years. Its abnormal expression is closely related to the biological behaviors of malignant tumors, such as cell proliferation, invasion, and migration. However, the specific mechanism of TMED3 in various tumors is very complicated. Here, the authors summarize the research status, mechanism, and clinical significance of TMED3 in malignant tumors, aiming to provide a reference for clinical and basic research of malignant tumors.