This study investigates the optimal operational parameters for oxidative degradation of orange II (OII) in heterogeneous chemical oxidation using CaMo0.67Cu0.33O3 perovskite catalyst. Response surface methodology– central composite design (RSM-CCD) experiments were used to optimize four critical operational parameters: catalyst dosage, initial concentration of OII dye, pH of solution and concentration of H2O2 on the percentage of OII removal. Based on the analysis of variance (ANOVA), the model illustrated a high correlation coefficient (R2 ) of 0.9941, which suggested that the empirical quadratic model fitted well to the experimental data. The optimal operational parameters were found to be at 0.99 g/L of catalyst dosage, 20.80 mg/L of initial concentration of OII dye, 5.42 pH solution and 0.87 g/L of H2O2 concentration. Interestingly, the experimental OII removal was found to be approximately 91.19% at the suggested optimal conditions. This experimental OII removal value aligns with the predicted value derived from the proposed quadratic model with a difference of 3.98%. Such findings have shown significant global interaction between four critical operational parameters towards OII removal during the heterogeneous chemical oxidation using CaMo0.67Cu0.33O3 perovskite catalyst.