Solid lipid nanoparticles (SLN) and nanostructured lipid carrier (NLC) have been employed in pharmaceutics and biomedical formulations. The present study focuses on the optimization of the production process of SLN and NLC by High Shear Homogenization (HSH) and High Pressure Homogenization (HPH). To build up the surface response charts, a 2(2) full factorial design based on 2 independent variables was used to obtain an optimized formulation. The effects of the production process on the mean particle size, polydispersity index (PI) and zeta potential (ZP) were investigated. Optimized SLN were produced applying 20,000 rpm HSH and 500 bar HPH pressure and NLC process 15,000 rpm HSH and 700 bar HPH pressure, respectively. This factorial design study has proven to be a useful tool in optimizing SLN (100 nm) and NLC (300 nm) formulations. The present results highlight the benefit of applying statistical designs in the preparation of lipid nanoparticles.