Abstract: Claudin-18 isoform 2 (Claudin18.2), a subtype specifically expressed within the Claudin18 family, is normally restricted to the differentiated epithelial cells of the gastric mucosa under physiological conditions. However, it is aberrantly overexpressed in various malignancies and plays a pivotal role in regulating tumor cell differentiation, proliferation, and migration. Immuno-positron emission tomography (immunoPET) and immuno-single-photon emission computed tomography (immunoSPECT) offer powerful, noninvasive modalities for evaluating Claudin18.2 expression in tumors, potentially enhancing diagnostic accuracy and informing personalized treatment strategies. This review summarizes recent advances in the development of radiopharmaceuticals targeting Claudin18.2 for diagnostic and therapeutic applications, outlines the challenges encountered in clinical translation, and discusses future research directions, aiming to provide some valuable reference for the clinical application and promotion of Claudin18.2-targeted therapies.