The effect of particle distribution non-uniformity on the microstructure and flow stress in nanostructured metal matrix composites produced by severe plastic deformation was investigated. The Al/SiC composite fabricated by accumulative roll bonding was considered as a case. Transmission electron microscope (TEM) and scanning transmission electron microscope (STEM) were used for microstructural characterizations. Based on the particle distribution, three different zones were considered: particle-free zone, single particle zone, and cluster zone. In comparison to the particle free zone, finer grain sizes with higher boundary misorientation angle were observed in the single particle zone. The lowest grain size (342/260 nm by TEM/STEM) was obtained in the cluster zone approximately between two near particles. The selected area diffraction showed the highest misorientation angle at these regions. A combined microstructure strengthening analysis was considered for the prediction of the flow stress. The flow stress is predicted based on the grain sizes at various microstructural zones, and the results were compared with the experimental yield stress of the composite.