The rate of many chemical and energy transformation processes depends on the kinetics of charge and mass transfer in porous electrodes, but rational design of efficient nanostructured electrodes is hindered by an inability to quantify effects of micro/nano-structures of real devices. Here we report a framework for detailed simulations conformal to 3D micro/nano-scale reconstructions of porous structures, obtained from phase-sensitive x-ray nanotomography, using COMSOL and iso2mesh packages coordinated with custom code for automated feature recognition, meshing, refinement, equation assignment, and solution. This computational framework is illustrated in visualizing 3D surface activity of an operating solid oxide fuel cell (SOFC) electrode under low and high bias along two important transport pathways (bulk and surface), showing the effect of local nanostructured morphology on global electrochemical response and demonstrating cathodic activation of bulk La1−x Sr x MnO3±δ (LSM). The methodology is flexible with possibilities for superimposition of mechanical, thermal, and other processes and for incorporation of inputs from multi-scale calculations. It has potential to serve as a platform for rational design of complex nanostructured hetero-foam devices with desired functionalities.