Over the next few years, it is expected that new, energetic, multifunctional materials will be engineered. There is a need for new methods to assemble such materials from manufactured nanopowders. In this article, we demonstrate a DNA-directed assembly procedure to produce highly energetic nanocomposites by assembling Al and CuO nanoparticles into micrometersized particles of an Al/CuO nanocomposite, which has exquisite energetic performance in comparison with its physically mixed Al/CuO counterparts. Using 80 nm Al nanoparticles, the heat of reaction and the onset temperature are 1.8 kJ g −1 and 410 °C, respectively. This experimental achievement relies on the development of simple and reliable protocols to disperse and sort metallic and metal oxide nanopowders in aqueous solution and the establishment of specific DNA surface-modification processes for Al and CuO nanoparticles. Overall, our work, which shows that DNA can be used as a structural material to assemble Al/Al, CuO/CuO and Al/CuO composite materials, opens a route for molecular engineering of the material on the nanoscale.