Nanosuspensions (NS) are novel means of delivering drugs in controlled manner used to enhance bioavailability and get controlled therapeutic effect. Thus, the aim of the current study was to develop and optimize the preparation and characterization methods of Nanosuspensions for poorly water-soluble drug compound Rosuvastatin Ca (ROS) using Box Behnken Design (BBD). Pre formulation studies included differential scanning Calorimetry (DSC), Infra-Red (FTIR) spectroscopy and X-Ray diffraction (XRD) analysis were carried out to check compatibility of ROS and other excipient before starting optimization modeling by Box Behnken Design. The designed fifteen formulae of Nanosuspension were prepared and monitored for different responses to determine optimum formula and its expected characterization parameters. Then testing the efficiency of optimum formula against selected responses. Rosuvastatin Ca (ROS) nano suspension formulating was prepared using thin film hydration method using Box Behnken Design modeling include three independent variables (cholesterol (X1), Soy lecithin (X2), and span 60 (X3)), The responses were coded Y1 to Y6 respectively (particle size (PS), zeta potential (ZP), entrapment efficiency percent (EE%), as well as in vitro drug release after four hours, eight hours, and twelve hours. After obtaining optimum formula it was monitored for responses Y1 to Y6. The values of studied responses were particle size (408.6 nm), zeta potential (-53 mv), entrapment efficiency (79.2 %), cumulative drug release at 4 hr (53.2 %), cumulative drug release at 8 hr (67.1 %) and cumulative drug release at 12 hr (86.8 %). The results demonstrated that BBD optimization technique succeeded in prediction of an optimized ROS NS formula which when prepared and investigated, it met the demands of the desired responses comparing with free Rosuvastatin.