Environmental pollution poses serious threats to ecosystems, human health, and overall quality of life. Among the most concerning pollutants are emerging contaminants like nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used in human and veterinary medicine. These drugs and their metabolites are excreted into wastewater systems, where existing treatment methods often fail to eliminate them fully. Due to their persistence in aquatic environments, NSAIDs accumulate, necessitating innovative degradation strategies. Fungal biotransformation offers a promising solution, using the unique metabolic capabilities of unicellular yeasts and filamentous fungi. This review explores the potential of fungi to degrade NSAIDs through various enzymatic and nonenzymatic pathways. It also highlights key challenges and perspectives in the field, such as understanding NSAID-fungal cell wall interactions, the role of transcriptional factors, and the regulatory networks involved in pharmaceutical biodegradation. The goal is to advance fungal-based strategies for more effective NSAID removal from wastewater, contributing to broader environmental remediation efforts.