Wastewater treatment, especially the efficient degradation of contaminants such as m-cresol, remains a pivotal challenge. This study investigates the application of artificial neural networks (ANN) in predicting total organic carbon (TOC) removal rates from m-cresol-contaminated wastewater by using the ultraviolet (UV)-Fenton oxidation process. Six key variables, namely, Fe 2+ dosage, H 2 O 2 dosage, catalyst quantity, reaction time, pH, and substrate concentration, were employed as inputs to the ANN model. Leveraging this multivariable input and a comprehensive data set, the ANN model projected a maximum TOC removal rate of 87.12%, validated by an efficiency of 86.26% achieved through experiments under the derived optimal conditions: Fe 2+ dosage at 16.09 mg/L, H 2 O 2 dosage at 1.40 mg/L, catalyst quantity at 0.11 g/L, reaction time of 29.80 min, initial pH of 3.66, and substrate concentration of 50 mg/L. Comparative analysis with other machine learning algorithms further revealed that the ANN model notably outperformed linear regression, support vector regression, and random forest in terms of precision. This work paves the way for resource-optimized experimental designs, fostering real-time wastewater monitoring and refining advanced oxidation process proficiency in industrial applications.