This study explored the synthesis of zeolitic imidazolate framework-67 (ZIF-67) nanoparticles using a microfluidic reactor, focusing on the effects of reactant concentration, temperature, and flow rate on the material’s properties. Design Expert software was utilized to optimize these variables to enhance the synthesis process while preventing reactor clogging due to precipitate formation. The experiments varied concentrations of cobalt (II) nitrate hexahydrate and 2-methylimidazole, along with temperature and flow rates. After synthesis, the samples underwent extensive characterization, including FTIR, NMR, TEM, SAED, and XRD analyses. FTIR results confirmed the successful formation of ZIF-67, with varying conditions leading to shifts in peak positions and intensities, indicating changes in bonding and molecular structure. NMR spectra provided insights into the hydrogen environments within the nanoparticles. TEM and SAED analyses revealed that the nanoparticles predominantly exhibited a uniform rhombic dodecahedral morphology with diameters ranging from 5 to 10 nm. XRD patterns were consistent with simulated data, showing variations in peak positions and crystallinity with changes in synthesis conditions. The study highlighted that increasing reactant concentrations, temperature, and flow rate generally enhanced the production rate and crystallinity of ZIF-67, with 2-methylimidazole concentration having the most significant impact. The findings contributed to optimizing ZIF-67 synthesis, demonstrating the feasibility of using microfluidic reactors and green solvents for producing high-quality nanoparticles with controlled properties.