Highlight our recent efforts in developing new molecularly-directed approaches to control the structure, chemistry, shape and functionality of nanostructures, their assemblies and interfaces, for applications in energy and nanoelectronics. I will first describe new surfactant-mediated techniques to sculpt nanocrystals of metal alloys and semiconductors with atomic-/molecular-level control over shape, surface chemistry and assembly configuration to realize novel properties and enhanced stability. Examples presented will include high-coercivity nanomagnets, molecularly braided nanoparticle strings, branched nanorods, rapid microwave synthesis of chalcogenide nanoplates and their assembly for realizing nanostructured bulk thermoelectrics with high figures of merit. I will then demonstrate the use of molecular nanolayers to obtain unprecedented enhancements in chemical stability and mechanical toughness of heterointerfaces. I will also show how this concept can be adapted to create adherent metal/polymer interfaces without a separate glue layer—an attribute that could be exploited for many energy and device applications. I will conclude with a first-time demonstration of experimentally accessing the nanomechanics of heterointerfacial fracture in a single molecular layer, paving the way for developing atomistic descriptions and the rational design of nanostructured heterointerfaces.