This study aimed to fabricate shellac (SHL) nanoparticles by optimizing the formulation and electrospraying process. We investigated the influence of formulation factors, including solvent types and SHL concentration, and process parameters like feed rate and applied voltage, on physical appearance, particle size, size distribution, and aspect ratio. Optimized conditions were determined using a Box–Behnken design. It was found that particle formation was significantly affected by the type of solvent, SHL concentration, applied voltage, and feed rate. Under the optimized conditions, uniform spherical nanoparticles were achieved. Overall, this study presents a simple and effective approach to producing nanoparticles as potential nanocarriers for drugs and related compounds in future applications.