Trametes polyzona is a white-rot basidiomycete with increasing relevance in environmental biotechnology due to its ligninolytic enzymes, biodegradation capacity, and versatile metabolic responses to diverse substrates. To provide an integrated and updated understanding of its biotechnological potential, we conducted a systematic review following PRISMA guidelines. A total of 46 studies published between 1991 and 2024 were analyzed, covering enzymatic production profiles, degradation of xenobiotics, extraction of bioactive metabolites, and experimental conditions influencing performance. Across the literature, T. polyzona consistently exhibits high ligninolytic activity, including laccase specific activities reported up to 1637 U/mg, together with efficient transformation of dyes, pesticides, and phenolic pollutants, and promising antioxidant and antimicrobial properties. However, substantial methodological heterogeneity was identified, particularly in strain characterization, fermentation parameters, and analytical approaches used to quantify enzymatic and biodegradation outcomes. These inconsistencies limit cross-study comparability and hinder process standardization. This review integrates current evidence; highlights critical gaps, such as limited ecotoxicological assessment of degradation products and scarce multi-omics characterization; and identifies key opportunities for process optimization in submerged/solid-state fermentation, bioreactor scaling, and the valorization of fungal metabolites. Overall, T. polyzona remains an underutilized resource with distinct advantages for applied mycology, environmental remediation, and industrial biotechnology.