Of the many research challenges in materials science is the development of more comprehensive methods for materials process design and control ranging from bulk materials transformation at the macro scale to increasingly small systems at the nano scale. The unavoidable frontier of the future is ‘small-systems’, wherein thin-films and MEMs are merely the bow wave to a world of atomic-scale ordering and transitions which will manifest in the interfacial designs of nano-functional building blocks for more portable and efficient systems. Although small-systems have widespread application to Air Force pursuits in becoming a Space Force, the technology will be inevitably driven by the need for more powerful but compact computing and telecommunication devices. Let us assume the inevitability of small-systems, and focus on the more immediate and prerequisite issues relative to materials research and the methods for design, analysis and control of processes to realize small-systems. To enable these methods will require investments - first, in the area of molecular modeling - transforming the various molecular modeling methods from their current use as a limited means of atomic-scale perusal to the simulation of growth processes for the manufacture of small-systems. Also at issue, and potentially more pivotal, is atomic-scale sensing for in situ monitoring of the deposition and self-assembly of nano-functional building blocks and their associated interfaces. We will need in situ, but non-destructive, methods for imaging surfaces and subsurface structures to assess defect densities, electrical, optical and thermal conductivities, size and continuity of granular orientations, etc.