A new microfluidic setup with impact-jet micromixers was built up and applied to control the nanoprecipitation process for generating polymeric nanoparticles and encapsulating a lipophilic drug. In contrast to a conventional nanoprecipitation processes in “bulk” phase, the microfluidic approach not only allows a continuous and controlled production of nanoparticles, but can also be used to manipulate and modify the nanoparticle size and the drug loading, by fine tuning the processing parameters. We developed a micromixer-assisted setup that can efficiently produce PMMA nanospheres, with a particle size of about 100 nm, and a narrow size distribution. Moreover, this setup enables a flow rate of the polymer phase as high as 1 mL min−1, opening the possibilities of large-scale production. The obtained nanoparticles can encapsulate high levels of a lipophilic drug (ketoprofen) and release it over 4 h. Finally, the solvent and non-solvent flow rates can be used to adjust the physicochemical and encapsulating/release properties of these nanosystems, opening new possibilities for nanoparticle production by nanoprecipitation.