Abstract: Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts in various epithelial tumors, but its expression is low in normal tissues. Therefore, FAP is considered as a potential target for tumor imaging and therapy. Some patients with differentiated thyroid cancer progress to metastatic radioactive iodine-refractory thyroid cancer (mRAIR-TC). mRAIR-TC is generally treated with tyrosine kinase inhibitor (TKI), but disease progression still occurs in some patients after TKI treatment, and the clinical management of these patients remains a major challenge. To clarify the potential value of FAP-targeted strategies in the theranostics of radioactive iodine-refractory thyroid cancer, the authors review their application value in such patients, based on the latest advances in clinical translational research.