Synthesis of nanoparticles and particulate nanomaterials with tailored properties is a central step toward many applications ranging from energy conversion and imaging/display to biosensing and nanomedicine. While existing microfluidics-based synthesis methods offer precise control over the synthesis process, most of them rely on passive, partial mixing of reagents, which limits their applicability and potentially, adversely alter the properties of synthesized products. Here, an acoustofluidic (i.e., the fusion of acoustic and microfluidics) synthesis platform is reported to synthesize nanoparticles and nanomaterials in a controllable, reproducible manner through acoustic-streaming-based active mixing of reagents. The acoustofluidic strategy allows for the dynamic control of the reaction conditions simply by adjusting the strength of the acoustic streaming. With this platform, the synthesis of versatile nanoparticles/nanomaterials is demonstrated including the synthesis of polymeric nanoparticles, chitosan nanoparticles, organic-inorganic hybrid nanomaterials, metal-organic framework biocomposites, and lipid-DNA complexes. The acoustofluidic synthesis platform, when incorporated with varying flow rates, compositions, or concentrations of reagents, will lend itself unprecedented flexibility in establishing various reaction conditions and thus enable the synthesis of versatile nanoparticles and nanomaterials with prescribed properties.,© 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.