The ability to manipulate miniature object assemblies with well-defined structures in a controllable manner is of both fundamental and applied interests. This article presents general strategies, with nanospheres as building blocks, to engineer mesoscopic spherical architectures via a process of evaporation-driven self-assembly in aerosol droplets. Uniform magnetite iron oxide (Fe3O4, similar to 2.5 nm), silica (SiO2, similar to 15 nm), and cupric oxide (CuO, similar to 6 nm) nanoparticles were employed for the structural architecture. The method enables microstructural control of the self-assembled mesospheres by tuning the competition between solvent evaporation and Solute diffusion within an aerosol droplet. Furthermore, we have demonstrated it is technically feasible to assemble surface-dissimilar binary components, i.e., charge-stabilized hydrophilic SiO2 and hydrophobic ligand-capped Fe3O4 nanoparticles, into hierarchical composite structures, which could,be extended for preparation of more hierarchically textured materials with desired functionalities.