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The use of various advanced oxidation methods in the treatment of wastewater has become the subject of many studies published in recent years. In particular, it is exceedingly significant to compare these treatment methods for industrial wastewater to reduce environmental effects and optimize plant operations and economics. The present study is the first to deal with the treatability of real epoxy paint wastewater (EPW) using MW- and UV-assisted Fenton processes within an optimization framework. A three-factor, three-level Box–Behnken experimental design combined with response surface methodology (RSM) was conducted for maximizing the chemical oxygen demand (COD) and color removal efficiencies of ultraviolet (UV)/Fenton and microwave (MW)/Fenton processes in the treatment of the real epoxy paint wastewater (EPW, initial COD = 4600 ± 90 mg/L, initial color = 114 ± 4 Pt-Co), based on 15 different experimental runs. Three independent variables (reaction time ranging from 20 to 60 min (UV) and from 5 to 15 min (MW), power ranging from 20 to 40 W (UV) and from 300 to 600 W (MW), and H2O2/Fe2+ ratio ranging from 0.2 to 0.6 (for both UV and MW)) were consecutively coded as A, B, and C at three levels (−1, 0, and 1), and four second-order polynomial regression equations were then derived to estimate the responses (COD and color removals) of two distinct systems. The significance of the independent model components and their interrelations were appraised by means of a variance analysis with 99% confidence limits (α = 0.01). The standardized differences of the independent variables and the consistency between the actual and predicted values were also investigated by preparing normal probability residual plots and experiment-model plots for all processes. The optimal operating conditions were attained by solving the quadratic regression models and analyzing the surface and contour plots. UV/Fenton and MW/Fenton processes, which constitute combined Fenton processes, were performed using advanced oxidation methods, while Fenton processes were utilized as the standard method for wastewater treatment. When UV/Fenton and MW/Fenton processes were applied separately, the COD removal efficiencies were determined to be 96.4% and 95.3%, respectively. For the color parameter, the removal efficiencies after the application of both processes were found to exceed 97.5%. While these efficiencies were achieved in 1 h with a 38 W UV unit, they were achieved in 15 min with a MW power of 570 W. According to the RSM-based regression analysis results, the R2 values for both processes were greater than 0.97 and p values were less than 0.003. [ABSTRACT FROM AUTHOR]