Functionalized iron oxide nanoparticles (IONPs) are of great interest due to wide range applications, especially in nanomedicine. However, they face challenges preventing their further applications such as rapid agglomeration, oxidation, etc. Appropriate surface modification of IONPs can conquer these barriers with improved physicochemical properties. This review summarizes recent advances in the surface modification of IONPs with small organic molecules, polymers and inorganic materials. The preparation methods, mechanisms and applications of surface-modified IONPs with different materials are discussed. Finally, the technical barriers of IONPs and their limitations in practical applications are pointed out, and the development trends and prospects are discussed.