In the present study, the synthesis of microporous zinc imidazolate nanoparticles was assessed with and without the presence of ibuprofen or 5-fluorouracil (5-FU) anticancer drug. The drugs loading was ensured by thermogravimetric analysis, nitrogen adsorption/desorption. The crystalline structure of the different prepared materials was monitored by using X-ray powder diffraction. Up to 5% loading (molar ratio of drug/Zn²⁺), there was no evidence of crystalline drugs in the XRD patterns, suggesting an optimized occupation of the ZIF-8 cells. The pattern of the samples remained identical with and without drug. Particle size ranging between 30 and 95 nm could be deduced according to the Scherrer equation. It was found to depend on the dilution of the reagents, but also on the presence of drugs in the synthesis medium. The morphology of the samples was presented by using scanning and transmission electron microscopies, confirming the size obtained using XRD. The presence of drugs induced a significant increase in the particle size of the synthesized materials; however, those sizes are still in range for drug delivery application (<200 nm). The drugs@ZIF-8 nanoparticles were found to be hexagonal or cubic shaped, depending on the reaction duration.