The design of scaffolds for critical-size bone defect treatment has been widely explored by targeting structural and mechanical properties such as porosity, pore size, specific surface area, and apparent elastic modulus. Nevertheless, optimal ranges for these parameters remain undefined, and current design methodologies continue to be refined. This work introduces a parametric scaffold design framework based on Voronoi tessellation, in which the microarchitecture is systematically controlled through a set of geometric parameters, including the density and spatial distribution of seed points, and the parameters controlling node size and strut thickness. Forty distinct microarchitectures (11x11x11 mm) were generated using Rhinoceros 8 (Robert McNeel & Associates, USA) and Grasshopper, and their structural properties were quantified enabling a direct correlation between design parameters and scaffold properties. Finite element simulations performed in ANSYS Workbench 19.2 (ANSYS, Inc., USA) were used to evaluate the apparent mechanical response. In parallel, micro-CT–based models of Merino sheep trabecular bone were segmented using Avizo (Thermo Scientific, Waltham, Massachusetts, USA) and simulated to identify scaffold architectures that most closely replicate native bone trabecular structure. The results showed that the density of seed points has a greater influence than any other parameter on porosity, specific surface area, and the apparent mechanical properties of the scaffold. In contrast, when the number of seed points (from 10 to 40) is kept constant, struct thickness (from 0.5 to 0.8 mm) has little impact on the mechanical and structural response, whereas the node size (from 0.5 to 0.6 mm) can respectively decrease or increase porosity and specific surface area by 30–40%.