The combustion of TiCl4 to synthesize TiO2 nanoparticles is a multimillion tonne per year industrial process. The objective of this paper is to further the understanding of this process. Work toward three aspects of this multiscale problem is presented herein: gas-phase chemistry, surface chemistry, and the solution of a multidimensional population balance problem coupled to detailed chemical mechanisms. Presented here is the first thermodynamically consistent mechanism with physically realistic elementary-step rate constants by which TiCl4 is oxidized to form a stable Ti2OxCly species that lies on the path to formation of TiO2 nanoparticles. Second, progress toward a surface chemistry mechanism based on density functional theory (DFT) calculations is described. Third, the extension of a stochastic two-dimensional (surface-volume) population balance solver is presented. For the first time, the number and size of primary particles within each agglomerate particle in the population is tracked. The particle model, which incorporates inception, coagulation, growth, and sintering, is coupled to the new gas-phase kinetic model using operator splitting, and is used to simulate a heated furnace laboratory reactor and an industrial reactor. Using the primary particle information, transmission electron microscopy (TEM)-style images of the particles are generated, demonstrating the potential utility of first-principles modeling for the prediction of particle morphology in complex industrial systems.