Materials at the nanoscale offer numerous avenues to be explored and exploited in diverse realms. Among others, proteinaceous biomaterials such as silk hold immense prospects in the domain of nanoengineering. Silk offers a unique combination of desirable facets like biocompatibility; extraordinary mechanical properties, such as elongation, elasticity, toughness, and modulus; and tunable biodegradability which are far better than most naturally occurring and engineered materials. Much of these properties are due to the molecular structure of the silk protein and it is self-assembly into hierarchical structures. Taking advantage of the hierarchical assembly, a large number of fabrication strategies have now emerged that allow the tailoring of silk structure of at the nanoscale. Harnessing the favorable properties of silk, such methods offer a promising direction toward producing structurally and functionally optimized silk nanomaterials. This review discusses the critical structure-property relationship in silk that occurs at the nanoscale and also aims to bring out the recent status in the approaches for fabrication, characterization, and the gamut of applications of various silk-based nanomaterials (nanoparticles, nanofibers, and nanocomposites) in the niche of translational research. Harnessing the favorable nanostructure of silk, the review also takes into account the impetus of silk in applications such as chemo-biosensing, energy harvesting, microfluidics, and environmental applications.