This paper reports a nanoscopic mechanosynthesis of three-dimensional (3D) nanostructures by nanolithography-based molecular manipulation (NMM) of target molecules for the applications requiring both physical and chemical anisotropies. The reported molecular manipulators with nanometer-sized patterns and anisotropic surface functionalities are fabricated by exploiting the hybrid nanometer-scale NMM process. They are then utilized for positional nanoassembly of molecules followed by mechanosynthesis producing 3D nanoreplicas. This approach offers "top-down" design and fabrication of morphological features of nanoparticles (NPs). Three types of replicated sub-10 nm polystyrene (PS) nanostructures have been successfully demonstrated in this work, namely, "nanomushrooms", "nanospikes", and high-aspect-ratio "nanofibers".