Abstract: Currently, there is controversy surrounding the definition of iodine-refractory differentiated thyroid cancer (RAIR-DTC). Its diagnosis is limited to evaluation after ¹³¹I therapy, and treatment options are quite restricted. Radioactive drug conjugates (RDCs) represent a class of precision-targeted drugs with radioactivity, offering new choices for the diagnosis and treatment of RAIR-DTC. The authors briefly introduce the molecular mechanisms of four categories of popular RDCs that target fibroblast activated protein, prostate specific membrane antigen, somatostatin receptor, and integrin αvβ3 receptor, and focus on their current research status in RAIR-DTC diagnosis and treatment, aiming to explore the value of RDCs in the management of RAIR-DTC and achieve integrated diagnosis and treatment.