<p>Landfill leachate contains high concentrations of ammonia, organic nitrogen, and per- and polyfluoroalkyl substances (PFAS), which seriously threaten the surrounding ecosystem and human health. The potential degradation of PFAS within conventional nitrification-denitrification, heterotrophic nitrification-aerobic denitrification, and Anammox-mediated systems will be summarized with focusing on the responses of various microorganisms to PFAS stress in the current review. A thorough analysis of landfill leachate composition is essential for selecting the appropriate treatment systems and anticipating the hurdles associated with their implementation. This review will show the key reasons that can impede the effectiveness of anammox-mediated systems, such as leachate composition, ambient temperature, and operating conditions, and recommend control strategies to address these challenges. The knowledge gaps in current research, prospects, and the challenges that need to be addressed to achieve a sustainable and robust treatment approach for the simultaneous removal of nitrogen and PFAS from leachate will be highlighted. This review emphasizes the current biological systems for nitrogen removal from landfill leachate, with a specific focus on the anaerobic ammonium oxidation (Anammox) process and its innovative combinations as promising solutions for achieving highly efficient nitrogen removal performance, PFAS removal, reducing greenhouse gas (GHG) emissions, and minimizing energy consumption.</p>