In this work, iron (II, III) oxide (Fe3O4) was synthesized and incorporated onto multi-walled carbon nanotubes (MWCNTs) to prepare Fe3O4-MWCNTs composite in a quest for evaluating its performance and reusability in both Fenton-like and photo-Fenton processes. The characterization of Fe3O4-MWCNTs by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, and energy dispersive X-ray (EDX) spectroscopy showed that the prepared catalyst can behave as a composite. Methylene blue (MB) was used as a substrate for evaluation of Fenton-like and photo-Fenton processes. The reusability of the catalyst and the influence of operation parameters such as pH, H2O2 dosage, and catalyst loading were investigated. Complete degradation of MB was attained by Fe3O4-MWCNTs in the aforementioned processes, whereas the removal efficiency of MB by using bare MWCNTs under the same conditions was 52%, which suggests that the generated oxidant species due to the reactions between H2O2 and leached iron contribute to the degradation of MB. A degradation pathway was proposed based on the oxidation intermediates that have been detected by mass spectrometry. The reusability of Fe3O4-MWCNTs has been examined in four consecutive cycles. The final removal of MB in the fourth cycle was 94%. The optimization of MB removal was investigated by response surface methodology (RSM) based on central composite design (CCD). Moreover, an artificial neural network (ANN) of type feed-forward back propagation was employed to model the influence of operating conditions. The ANN model revealed a high correlation in the prediction of the removal efficiency (R-2 = 0.9934). (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.