The escalating release of synthetic xenobiotics from industrial, pharmaceutical, and agricultural activities has created unprecedented environmental contamination challenges. Mycoremediation, utilizing fungi for environmental detoxification, offers a sustainable biotechnological solution to address persistent organic pollutants, pharmaceutical residues, and agricultural chemicals. White-rot fungi, particularly Phanerochaete chrysosporium and Trametes versicolor, possess unique extracellular enzymatic systems, including lignin peroxidases, manganese peroxidases, and laccases, that enable broad-spectrum xenobiotic degradation. These nonspecific oxidative enzymes, combined with intracellular cytochrome P450 monooxygenases, facilitate the transformation of structurally diverse contaminants that resist conventional biological treatments. Field applications demonstrate mycoremediation’s effectiveness across diverse contamination contexts, from European industrial sites to North American agricultural soils and Asian pharmaceutical effluents. While challenges remain in optimizing environmental conditions and scaling laboratory results to field applications, mycoremediation represents a cost-effective, ecologically sustainable approach that integrates pollution remediation with circular economy principles, positioning fungi as powerful allies in global environmental restoration efforts.