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With the rapid advancement of nanotechnology and with nanoparticles beginning to enter into products, the demand for production-level quantities of advanced nanopowders such as multi-component or coated oxides is rising. Such advanced nanoparticles can be effectively made by flame spray pyrolysis (FSP), and research with laboratory reactors yielded a spectrum of new nanomaterials for catalysis, pigments, ceramics, optics, energy and biomaterials, among others. Here, the transfer of FSP nanopowder synthesis from gram-level lab-scale to pilot reactors with up to 10 metric tons annual production rate is investigated by the example of FSP pilot plants that were realized in industrial-oriented settings. Design considerations for such pilot-scale systems are addressed and guides to production cost estimates are given. Special attention is brought to safe and contained nanoparticle manufacture in order to address the growing awareness of the potential health and environmental effects of nanoparticles.