Nanosphere lithography, a low-cost fabrication technique, depends on the self-assembly of nanoscale features to create nanostructures in a hexagonally close-packed structure. In this article, the fabrication of 3D nanostructures over a large surface-area with anisotropy along the growth direction through the combination of chemical and physical plasma etching is reported. The anisotropy stems from etching the nanosphere mask and the substrate at different rates. Due to the dynamic masking effect, a systematic variation of etching time gives rise to intriguing nanostructures with sharp edges that have strong potential for plasmonic applications, with the possibility of manipulating electromagnetic radiation. The structures obtained include nanocylinders, truncated hexagon-based pyramids, circular pads on a conical base, and nanocones from a single-layer nanosphere mask. Simulations of the fabrication process offer further insight into the understanding of nanostructure formation. A good agreement between predicted results and experiments confirms the potential of our numerical design. In addition, the optical properties of the nanostructures are investigated by UV–vis and the experimental findings are consistent with simulations based on a finite-difference time-domain method. The nanostructures described in this study contribute to the emerging 3D plasmonics and 3D magnonics, with strong potential for a significant impact on biosensor applications.