Anaerobic ammonium oxidation (ANAMMOX) has emerged as a promising sustainable nitrogen removal technology that offers significant advantages over conventional nitrification–denitrification processes, such as reduced energy consumption, a 60% reduction in oxygen demand, and a 90% reduction in sludge production. However, the practical application of ANAMMOX is hindered by several challenges, including the slow growth of ANAMMOX bacteria, long start-up periods, and high sensitivity to environmental disturbances. Recent studies have highlighted the crucial role of extracellular polymeric substances (EPSs) in the formation, activity, and stability of ANAMMOX biofilms and granules. An EPS is a complex mixture of high-molecular-weight polymers secreted by microorganisms, mainly composed of polysaccharides, proteins, nucleic acids, and lipids. The diverse physicochemical properties and functional groups of EPSs enable them to serve as a structural scaffold, protective barrier, sorption site, electron shuttle, and nutrient source for ANAMMOX bacteria. This review aims to provide an overview of the latest research progress on harnessing the potential of EPSs to enhance the ANAMMOX process. The characteristics, compositions, and extraction methods of ANAMMOX-derived EPSs are summarized. The mechanisms of how EPSs facilitate the enrichment, immobilization, aggregation, and adaptation of ANAMMOX bacteria are elucidated. The strategies and effects of EPS supplementation on improving the performance and robustness of ANAMMOX reactors under various stresses are critically reviewed. The challenges and future perspectives of the EPS-mediated optimization of the ANAMMOX process are also discussed. This review sheds new light on exploiting EPSs as a renewable bioresource to develop more efficient and stable ANAMMOX applications for sustainable wastewater treatment.