Abstract: Claudin18.2 (CLDN18.2) is highly expressed in various solid tumors, including gastric and pancreatic cancers, while its expression is low or absent in most normal tissues, making it an important tumor-specific target. The authors systematically review the structure, functions, and tissue distribution of CLDN18.2, CLDN18.2-targeted therapeutic strategies, and recent advances in CLDN18.2-targeted imaging for cancer diagnosis and treatment. Taken together, this review provides new strategies and insights for establishing CLDN18.2 as a key target for theranostics.