In situ combustion is an advanced recovery technique used to exploit heavy oil in the fractured reservoirs that make up approximately one-third of global heavy-oil resources. However, the mesoscopic mechanisms of coke combustion in the multiscale matrix-fracture system are not well understood because of the difficulty of performing pore-resolved simulations. In the present study, a pore-resolved micro-continuum approach was used to investigate fully coupled thermal and reactive flows through fractured media that contain nanometer-range coke pores, micrometer-range matrix pores, and sub-millimeter range natural fractures. Image-based simulations were implemented using synthetic geological models to mimic coke deposition patterns based on tomography images. The combustion regime diagram for the fractured media was mapped based on the ignition temperature and the air flux to exhibit three combustion regimes. The regime diagram was compared with that for unfractured media to address the impact of natural fractures on oxygen transport and the burning temperature. The oxygen diffusion mechanism dominated oxygen transport from the fracture into the matrix and led to a desirable smoldering combustion temperature regardless of the air injection rate. Effects of fracture geometries were quantified to demonstrate tortuous and discrete fractures, and matching air injection rates with fracture apertures can suppress air-channeling risk effectively. Possible discrepancies between lab measurements and field operations were demonstrated, and their potential to drive misinterpretation of experimental results was considered. The present pathway from tomography images to synthetic images and numerical simulations extends the “image and compute” technique to resolution of multiscale and nonlinear reactive transport.