How surface geometries can be selectively manipulated through nanosphere lithography (NSL) is discussed. Self-assembled monolayers and multilayers of nanospheres have been studied for decades and have been applied to lithography for almost as long. When compared to the most modern, state-of-the-art techniques, NSL offers comparable feature resolution with many advantages over competing technologies. Several high-resolution alternatives require scan-based implementation (i.e., focused ion beams and e-beam lithography) while NSL is much more of a batch operation, allowing for full wafer or possibly even multiple wafer processing, potentially saving time and increasing throughput in a manufacturing environment. Additionally, NSL has continued to be of interest because it does not require expensive, complex equipment to be researched and realized, which continues to fuel interest in this approach. In spite of these advantages, applying NSL to specific, realizable devices is limited in the literature. The reason for this lack of application is not only unreliability in the self-assembly process, but also control of these patterned nanospheres within larger, multistep processes often required to fabricate most devices. Both of these items are addressed in this paper. The first issue was addressed through the development of a series of custom-designed nanosphere application vessels. These were designed based on the best published results from the literature, utilizing an alternate method of dip-coating but performed through draining the carrier fluid over the substrate rather than moving the substrate across the liquid–air boundary layer. This method is in the easier to perform, but arguably less-reliable spin-coating method also commonly employed. The key enabler in this effort lies in commercially available three-dimensional (3-D) printing technology, and how it was applied to rapidly prototype-improved deposition vessels. This was accomplished primarily with a single day turn-around between each 3-D printed design iteration. Each vessel design was incrementally improved, built, and tested to optimize the best performance in achieving the most reliable, repeatable self-aligned nanosphere layer formation. With an optimized design of this vessel in hand, the second challenge was addressed by using this vessel and the patterned nanosphere layers it produced with a patterned photoresist design to capture single layers of nanospheres in specifically designed locations and orientations. The hybrid mask produced from this approach can be integrated within virtually any multistep fabrication process. Additionally, other processing steps will be discussed, such as reactive ion etching (RIE), plasma ashing, and photoresist reflowing, and how they might be combined with these hybrid masks. Various results from combinations of these steps are presented. Finally, two potential applications which could benefit greatly from the resulting, engineered surface structures are discussed. These include a small-scale device application (engineering the contacting surfaces in a microswitch), as well as a much larger scale surface study application (surface engineering for controlling secondary electron emissions). The final results from this method allow for patterning groups of 500-nm polystyrene nanospheres formed in four to eight distinct rows each. These are positioned within patterned wells created in a 650-nm thick photoresist. The size and location of these wells are as precise as the photolithography process used to form them, in this case, position error in the location of the edge of the laser using a Heidelberg laser lithography system. By combining multiple wells in close proximity, virtually any combination of nanosphere clusters become possible. Once patterned, postprocessing though RIE and deposition method selection together determine the final shape of the nanoscale features which result.