To understand the nanoparticle formation of quercetin in the poly-lactic-co-glycolic acid/water system, a multiscale approach combining experimental, molecular, and mesoscale modelings was carried out. The evolution of interactions occurring between compounds mixed at different ratios was evaluated by the order parameter, calculated using MesoDyn simulations. The obtained results indicated that the studied systems allowed to produce spherical nanoparticles well distributed in the continuous medium (water). The fast kinetics of nanoparticle formation is reached with 10 g L-1 of poly-lactic-co-glycolic acid, 0.5 g L-1 of quercetin, and 0.5% of polyvinyl alcohol. The corresponding order parameter of water (P-water) was equal to 0.018. The increase of poly-lactic-co-glycolic acid and quercetin concentrations and the lactic acid content in poly-lactic-co-glycolic acid favor the formation of nanoparticles with a large size. The formed nanoparticles were composed of quercetin in the center of the system, poly-lactic-co-glycolic acid, as the second layer, and polyvinyl alcohol as the third layer. The water is the continuous phase. The shape, the size, and the order organization of nanoparticles were checked experimentally using transmission electron microscopy and dynamic light scattering. The obtained results indicated that experimental investigations are in good agreement with the simulated ones. Therefore, computational mesoscopic modeling can be used as a successful tool to predict the behavior of quercetin/poly-lactic-co-glycolic acid/water systems under different operating conditions.