<p>Polystyrene is a widely utilized petroleum-derived thermoplastic, appreciated for its low cost, lightweight nature, and favorable thermal and mechanical properties. Nevertheless, its inherent hydrophobicity, chemical inertness, and non-biodegradability limit its performance in advanced applications and create environmental and recycling challenges. Post-polymerization functionalization offers a versatile approach to overcome these limitations, enabling enhanced chemical reactivity, tunable physicochemical properties, and sustainable reuse. This review provides a comprehensive overview of PS functionalization strategies, including electrophilic aromatic substitution (nitration, sulfonation, acylation, halogenation), nucleophilic and radical grafting (maleic anhydride grafting, ATRP, nitroxide-mediated polymerization), click chemistry (azide-alkyne cycloaddition), and chain backbone modifications (photochlorination, radical additions). Representative functional groups such as -NO₂, -SO₃H, -COAr, -CH₂X, -NH₂, -CH₂N₃, -B(OR)₂, and halogens are highlighted, alongside the relevant reagents, catalysts, and reaction conditions. Functionalized PS has been successfully applied as polymer-supported catalysts, scavengers, chelating adsorbents, proton exchange membranes, polymer blend compatibilizers, redox-active materials, and DNA-binding probes, demonstrating its versatility across catalysis, environmental remediation, energy storage, and biomedical applications. Challenges persist in achieving uniform modification, minimizing degradation, and scaling eco-friendly processes. Future directions emphasize the development of green, non-toxic, and economically viable functionalization methods, the integration of multi-functional and click-chemistry-based modifications, and the implementation of circular economy strategies to transform PS into high-value, sustainable materials.</p>