Copper and nickel were incorporated into the prepared yellow clay (YC) using one of the most widely used methods, for the preparation of heterogeneous catalysts, which is the wet impregnation method (IPM) and its application as a heterogeneous catalyst for Caffeine (CAF). Several catalysts Cooper Nickel's Catalysts (Cu-Ni) were applied to the yellow clay with different weight ratio of Cu and Ni, in order to explore the role of both metals during the catalytic oxidation process CWPO. Furthermore, the CuNi-YC catalysts, were characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), Langmuir's surface area, Brunauer Emmett Teller (BET), scanning electron microscope (SEM) and inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES), so as to get a better understanding concerning the catalytic activity's behavior of CuNi-YC catalysts. The optimization of the catalytic activity's effects on the different weight ratios of Cu and Ni, temperature and H 2 O 2 were also examined, using Box-Behnken Response Surface Methodology RSM to enhance the CAF conversion. The analysis of variances (ANOVA) demonstrates that Box-Behnken model was valid and the CAF conversion reached 86.16%, when H 2 O 2 dosage was equal to 0.15 mol.L À1 , copper impregnated (10%) and temperature value attained 60 C. In addition, the regeneration of catalyst's cycles under the optimum conditions, indicated the higher stability up to four cycles without a considerable reduction in its conversion performance.