This investigation utilizes quality-by-design approach to develop the Rosuvastatin Calcium (Rst)-loaded solid lipid nanoparticles (SLN). Effect of formulation variables such as amount of lipid (200-500 mg stearic acid) and surfactant concentration (0.5-2.0% PVA) were studied. Design of Experiment (DoE) was used to quantify the extent of impact of lipid amount and surfactant concentration on the physicochemical properties of the SLN and to identify optimized SLN formulation. It was observed that interplay of formulation variables had significant effect on particle size (198.25 to 622.36 nm), %EE (28.82 to 35.87%) and In vitro release (44.87 to 64.29%). Based on the results, point optimization was carried out to obtain the SLN with minimum particle size (202.5 ± 9.29 nm), maximum %EE (34.78 ± 0.37 %) and sustained In vitro release (57.3 ± 2.6 % at 36 hours) within the design space. In vitro drug release data fitted well in Korsmeyer-peppas model indicating the fickian diffusion mechanism. Ex vivo studies indicated sustained permeation of the Ropt compared to the control. Furthermore, stability studies indicated Ropt formulation exhibited no significant physical or chemical change under accelerated conditions.