The coring data in high water‐cut oilfields indicates that the reservoir permeability will change continuously with water flooding, while the existing reservoir numerical simulation software cannot consider the time‐varying phenomenon of permeability. With the enhancement of reservoir heterogeneity, the near‐wellbore profile control fails to stabilize the oil production and control the water cut. The in‐depth profile control has been widely used in oilfields as a new technology, and the types of profile control agents are diverse, with a complex mechanism that cannot be effectively described by the existing conventional numerical simulation software. Considering these two phenomena comprehensively, a new three‐dimensional, three‐phase, six‐component mathematical model that can take into account the time‐varying phenomenon of reservoir permeability is proposed for a new kind of in‐depth profile control system, namely, the core–shell coagulation system, and an integrated numerical simulation software is developed. The mechanism of the in‐depth profile control system can be perfectly demonstrated in the simulator with time‐variation of permeability. The results of sensitivity analysis show that the effect is influenced by three factors: the mix slug injecting concentration, the coagulant aid slug volume, and the concentration of the suspension dispersing agent.