Throughout the previous decade, extensive advancements have been made in the field of nanomaterial synthesis via laser ablation synthesis in solution (LASiS). In this technique, a solid target is ablated using high-intensity pulsed laser irradiation while immersed in a liquid. This “green” technique allows ligand-free nanoparticles (Nps) to be fabricated without the need for environmentally harmful solvents, paving the way for the production of chemically pure surface coatings. LASiS allows for an in-situ, single-step and post-production surface functionalization, enabling its use in areas such as chemical separation, biosensing, cellular labelling, display technology. Despite these advances, the challenge of reliable production scale-up from batch to continuous production has yet to be realized. A current approach to LASiS scale-up has been to increase average laser power, while minimizing pulse width, resulting in an increased nanoparticle production rate. However, this route on its own has struggled to bridge the commercialization gap with chemical techniques due to the high capital costs of high-power laser systems. In this work, LASiS scale-up has been implemented under continuous flow conditions using low-powered micro-machining laser systems. A 3D printed Nps flow-cell reactor was developed, along with the application of real-time monitoring and control tools to enable autonomous nanoparticle production and characterization. The quality of nano-colloids produced was determined in real-time via atline process analyzers, including dynamic light scattering (DLS) and UV-vis spectroscopy. At-line measurements were validated versus off-line characterization tools, including Transmission Electron Microscopy (TEM). Process optimization of the developed system yielded the highest Np production efficiencies to date in reported in literature for gold, silicon and zinc oxide nanoparticles. This work concludes that high-efficiency, low-cost laser systems can produce Nps that are comparable with wet chemical synthesis, while maintaining the environmental and functional advantages of the LASiS technique.