This paper presents computational and experimental studies of a vanadium microfluidic fuel cell using a novel configuration of multi-layer flow-through porous carbon paper electrodes. A priori modeling, and simulation revealed that these porous substrates operated with non-uniform reaction rate and the reaction rate distribution is highly sensitive to the flow rate condition. Comparable cell performance was witnessed for electrodes partly modified in the high reaction rate region and electrodes modified in all parts. Therefore, multi-layer stacking of single-layer electrodes was proposed and implemented to facilitate selection of appropriate materials to accommodate the requirements of the different layers of the electrodes. Here, the electrode materials studied were pristine carbon paper and electrochemically superior platinum coated carbon paper. The results stemmed from modeling and experiments consistently revealed that the highest peak power densities were obtained in the case with electrode modification in the high reaction rate region. This study highlights the significance of the multi-layer electrode configuration associated with the balance between performance and cost of this energy-system. Moreover, the multi-layer electrode configuration offers flexibility in terms of changing layer arrangement to cope with the operating condition leading to superior cell performance. (C) 2016 Elsevier Ltd. All rights reserved.