The process of the fluid catalytic cracking (FCC) is accompanied by complex physical and chemical reactions and phase transition processes. For the FCC process–maximizing isoparaffin process (MIP), coupled simulation and optimization of flow reaction can meet the requirements for the design and operation of high efficiency, low energy consumption, low pollution, and low cost in the catalytic device. A combination of Eulerian–Eulerian model and 11-lump kinetic model is adopted to simulate the flow-reaction process of gas–solid two-phase of an industrial MIP riser reactor. A drag model based on the energy-minimization multiscale model established by Yang is incorporated into FLUENT through a user-defined function (UDF). The temperature distribution of the catalyst and the concentration of each product component at the outlet are in good agreement with the industrial measured data, which indicates that the established coupling model of flow reaction and drag model are reliable and effective. The two operating variables of the catalyst-to-oil ratio and catalyst inlet temperature are explored their effects on the flow-reaction process of FCC gas–solid two-phase. In the prelifting zone, the velocity of catalyst particles presents parabolic distribution. In the first reaction zone, the maximum velocity of catalyst particles is about 1/2 of the radius of the riser. In the second reaction zone, the maximum particle velocity of catalyst is located in the central region, with a slight increase in about 1/2 of the radius of the riser. The increase in catalyst-to-oil ratio leads to the decrease in the yield of diesel oil and the increase in yields of gasoline, liquefied petroleum gas, propylene, and dry gas. The changes in the catalyst inlet temperature affect the product distribution of the outlet component, which can provide an important guiding significance.