Abstract: The tight junction protein claudin 18.2 (CLDN18.2) is abnormally overexpressed in gastric cancer, pancreatic cancer and other malignant tumors. Due to its high tissue specificity, extensive patient coverage and the potential of multiple technical pathways, it has become a new focus in the field of cancer treatment. In recent years, significant breakthroughs have been made in the development of innovative drugs targeting CLDN18.2, especially the first antibody drug targeting CLDN18.2, zolbetuximab, which was approved in Japan in 2024, marking a new stage in CLDN18.2 targeted therapy. This article reviews the biological basis of CLDN18.2 as a tumor treatment target, with a focus on the research progress of antibody drug, antibody drug conjugate (ADC), chimeric antigen receptor T-cell (CAR-T) therapy, and radionuclide drug conjugate (RDC) for this target, with the aim to provide reference for the further development and clinical application of CLDN18.2 targeted drugs.