The existing modeling methods for lysine production usually ignore the complex reaction mechanism, lacking microbial insights into intracellular behavior. In this paper, a novel integrated modeling strategy is presented by combining the macrokinetics with the metabolic network. The integrated model is built on the reduced metabolic network of Corynebacterium glutamicum, which describes the kernel metabolic pathways including glycolysis, TCA cycle, product generation, and oxidative phosphorylation. The macrokinetics of biomass, product, and substrate are then represented by differential equations respectively, of which the kinetic coefficients are coupled with the metabolic flux balance equation. Therefore, the unknown model parameters are searched by an intelligent genetic algorithm. Using the experimental data, the proposed modeling method is demonstrated and discussed in three different scenarios. The results reveal that the model presented in this research precisely agrees with the experimental data and provides quantitative micro insights into the cell fluxes.