This study investigated chemical oxygen demand (COD) removal from tannery wastewater (TWW) with a novel Fe3O4/Mn3O4/ZnO-rGO heterogeneous electro Fenton (HEF) hybrid magnetically-separable nano-catalyst. The graphite cathode and Ti/IrO2/RuO2 anode were used in the HEF process. With aeration (2 L/min), in-situ H2O2 generation occurred. The nano-catalyst was characterized by XRD, XPS, DES, FT-1R, zeta potential, SEM, TEM, and BET techniques in detail. The system was modelled with a central composite design and optimized numerically. The established model was adequate, valid, reliable, and reproducible to predict the COD removal efficiency. center dot OH and center dot O-2(-) were the oxidative species responsible for organic matter degradation. The effect of different processes was investigated, and efficiency was ranked from high to low as; HEF > anodic oxidation-H2O2 > anodic oxidation > adsorption. Under the optimum conditions; pH: 3.5, current density: 7.37 mA/cm(2), reaction time: 79.43 min, and catalyst dose: 0.06 g/L, COD removal efficiency reached a maximum of 97.08%. The energy consumption and cost to remove 1 kg COD were 10.87 kWh and $1.41. The degradation of COD fitted the pseudo-first-order model. The nano-catalyst was stable and reusable with a minimum yield of 78.12% after 5 cycles.