In this era of the Internet of Things, the development of innovative sensors has rapidly accelerated with that of nanotechnology to accommodate various demands for smart applications. The practical use of three-dimensional (3D) nanostructured materials breaks several limitations of conventional sensors, including the large surface-to-volume ratio, precisely tunable pore size and porosity, and efficient signal transduction of 3D geometries. This review provides an in-depth discussion on recent advances in chemical and mechanical sensors based on 3D nanostructures, which are rationally designed and manufactured by advanced 3D nanofabrication techniques that consider structural factors (e.g., porosity, periodicity, and connectivity). In particular, we focus on a proximity-field nanopatterning technique that specializes in the production of periodic porous 3D nanostructures that satisfy the structural properties universally required to improve the performance of various sensor systems. State-of-the-art demonstrations of high-performance sensor devices such as supersensitive gas sensors and wearable strain sensors realized through designed 3D nanostructures are summarized. Finally, challenges and outlooks related to nanostructures and nanofabrication for the practical application of 3D nanostructure-based sensor systems are proposed.