Recent work indicates that materials with nanoscale architectures, such as nanolayered Cu-Nb composites and nanoscale oxide dispersion-strengthened steels, are both thermally stable and offer improved performance under irradiation.Current understanding of the atomic-level response of such materials to radiation yields insights into how controlling composition, morphology and interface-defect interactions may further enable atomic-scale design of radiation tolerant nanostructured composite materials. With greater understanding of irradiationassisted degradation mechanisms, this bottom-up design approach may pave the way for creating the extreme environment-tolerant structural materials needed to meet the world's clean energy demand by expanding use of advanced fission and future fusion power.2