Separate-layer fracturing with temporary plugging (SLFTP) is a potential way to stimulate multiple layer reservoirs due to its low cost, low risk, and high efficiency. In this study, based on the cohesive zone model (CZM), a 3D fully fluid-solid coupling and multiple layer model is established to investigate factors influencing fracture injection pressure and fracture mouth width. The cohesive layer properties are based on the reported study, which have been validated through a series of numerical experiments. Innovatively, the spring model is innovatively proposed to represent the plugging effect of diverting agents and prop the aperture of the previous fractures. Simulation results reveal that the effects of previous fractures in multiple layer formations can be neglected, which is quite different from multistage fracturing for horizontal wells. Fracture injection pressure can be evaluated more accurately by taking the following factors into consideration: the minimum horizontal principal stress, rock tensile strength, injection rate, and pore pressure enhancement. Further, fracture mouth width is strongly influenced by rock tensile strength, Young’s modulus, and injection rate. This study provides a guidance for candidate well selection and diverting agent optimization during SLFTP in multilayer formations.