The removal of per- and polyfluoroalkyl substances (PFAS) in complex waste streams remains an urgent environmental challenge due to their persistence and resistance to conventional treatment methods. This study investigates the performance of five PFAS-selective adsorbents: three cyclodextrin-based polymers, a hydrogel, and a polymer-metal oxide hybrid against traditional granular activated carbon (GAC) and ion exchange (IX) resins. While previous studies have examined PFAS removal in idealized conditions, the performance of these PFAS-selective adsorbents in complex real-world waste streams remain largely unexplored. This study presents the first comprehensive evaluation of emerging PFAS-selective materials across five distinct and challenging waste matrices (e.g., nanofiltration retentates and wet scrubber wastewaters), providing critical insights into their practical applicability. Overall, the PFAS-selective adsorbents exhibited faster adsorption kinetics and higher PFAS removal efficiencies in these complex matrices. The key to this enhanced performance is designing the interplay of multiple factors – including electrostatic attraction and hydrophobic capture, as well as pore configuration or fluorophilic interactions – that lead to higher affinity for PFAS removal. Mechanistic desorption studies demonstrated that a solvent-salt combination significantly improves PFAS recovery rates, up to 225-fold higher than single-component regenerants. These findings suggest a pathway toward sustainable PFAS remediation, minimizing environmental impact by enabling adsorbent reuse. Overall, the study highlights the high potential of these novel adsorbents to enhance PFAS management in diverse aqueous environments. Future work should focus on refining adsorbent formulations and regeneration protocols to maximize their practical application and adaptability to regulatory frameworks and environmental contexts.