From an environmental engineering perspective, dye-contaminated effluents require efficient and statistically optimized treatment processes to reduce aquatic pollution and improve wastewater treatment performance. This study investigated the statistical optimization of methylene blue (MB) removal from aqueous solution using a UV-A-assisted Fenton process based on Fe²⁺/H₂O₂ oxidation. Iron (II) sulfate heptahydrate (FeSO₄·7H₂O) was used as the Fe²⁺ source, while hydrogen peroxide (30% w/w) was employed as the oxidant. Response Surface Methodology (RSM) coupled with a three-factor Box–Behnken Design (BBD) was applied to evaluate the effects of A: ratio [Fe²⁺]/[H₂O₂] (0.15–0.35), B: reaction time (15–205 min), and C: temperature (20–40 °C) on MB degradation efficiency. The initial pH was fixed at 3 to ensure suitable conditions for Fenton oxidation. Experiments were performed in a batch photoreactor placed in a closed dark chamber under UV-A irradiation centered at approximately 365 nm. The experimental MB removal efficiencies ranged from 54.81% to 80.90%, confirming the strong influence of operating conditions on the oxidation process. The quadratic model was statistically significant, with F = 18.81 and p = 0.0024, and showed good predictive performance, as demonstrated by R² = 0.9713, adjusted R² = 0.9197, and predicted R² = 0.8440. The lack of fit was not significant (p = 0.8884), confirming model adequacy. Analysis of variance showed that the [Fe²⁺]/[H₂O₂] ratio and temperature were the most influential factors, while the quadratic effects of A² and C² were also significant. Numerical optimization predicted optimum conditions of A = 0.15, B = 15 min, and C = 40 °C, giving 81.61% MB removal with a desirability of 0.90. Experimental validation under these conditions achieved 79.23% removal, confirming the reliability of the RSM-BBD model for optimizing advanced oxidation processes in dye-contaminated wastewater treatment.