The scale-up of nanoparticle synthesis by a versatile flame aerosol technology (flame spray pyrolysis) is investigated numerically and experimentally for production of ZrO2. A three-dimensional computational fluid dynamics model is developed accounting for combustion and particle dynamics by an Eulerian continuum approach coupled with Lagrangian description of multicomponent spray droplet atomization, transport, and evaporation. The model allows the extraction of the high-temperature particle residence time (HTPRT) that is governed by the dispersion gas to precursor liquid mass flow ratio as well as the flame enthalpy content. The HTPRT is shown to control the primary particle and agglomerate size, morphology, and even ZrO2 crystallinity in agreement with experimental data. When the HTPRT is kept constant, the production rate for ZrO2 nanoparticles could be scaled up from similar to 100 to 500 g/h without significantly affecting product particle properties, revealing the HTPRT as a key design parameter for flame aerosol processes.