Melamincyanurate microcrystals suspended in water were converted into colloidal nanoparticles by a novel approach approach of ultrasound-assisted laser fragmentation in a free liquid jet. A crucial step within the laser-based synthesis is the sufficient stabilization of nascent nanoparticles with an adequate stabilization agent. Electron microscopy of stabilized and unstabilized nanoparticle colloids revealed that insufficient stabilized colloids contain a huge fraction of agglomerates consisting of nanoparticles adsorbed on microparticles. Those agglomerates could be destroyed by ultrasound sonication. Therefore, an implementation of ultrasonication into the laser fragmentation process enhances efficiency which was quantified by absorption spectra. By using a high-power nanosecond laser we demonstrated that the technique of laser-fragmentation in free liquid jet could be suitable for scale-up because nanoparticle properties like hydrodynamic size or zeta potential did not depend on laser power or process time and laser-fabricated nanoparticle yield continuously increases during process duration.