Nanostructured materials are being actively developed, while it remains an open question how to rapidly scale them up to bulk engineering materials for broad industrial applications. This study propose an industrial approach to rapidly fabricate high-strength large-size nanostructured metal matrix composites and attempts to investigate and optimize the deposition process and strengthening mechanism. Here, advanced nanocrystalline aluminum matrix composites (nanoAMCs) were assembled for the first time by a novel nano-additive manufacturing method that was guided by numerical simulations (i.e. the in-flight particle model and the porefree deposition model). The present nanoAMC with a mean grain size <50 nm in matrix exhibited hardness eight times higher than the bulk aluminum and shows the highest hardness among all Al–Al2O3 composites reported to date in the literature, which are the outcome of controlling multiscale strengthening mechanisms from tailoring solution atoms, dislocations, grain boundaries, precipitates, and externally introduced reinforcing particles. The present high-throughput strategy and method can be extended to design and architect advanced coatings or bulk materials in a highly efficient (synthesizing a nanostructured bulk with dimensions of 50 × 20 × 4 mm3 in 9 min) and highly flexible (regulating the gradient microstructures in bulk) way, which is conducive to industrial production and application.