Gas injection is one of the most effective enhanced oil recovery methods for the unconventional reservoirs. Recently, CH4 has been widely used; however, few studies exist to accurately evaluate the cyclic CH4 injection considering molecular diffusion and nanopore effects. Additionally, the effects of operation parameters are still not systematically understood. Therefore, the objective of this work is to build an efficient numerical model to investigate the impacts of molecular diffusion, capillary pressure, and operation parameters. The confined phase behavior was incorporated in the model considering the critical property shifts and capillary pressure. Subsequently, we built a field-scale simulation model of the Eagle Ford shale reservoir. The fluid properties under different pore sizes were evaluated. Finally, a series of studies were conducted to examine the contributions of each key parameter on the well production. Results of sensitivity analysis indicate that the effect of confinement and molecular diffusion significantly influence CH4 injection effectiveness, followed by matrix permeability, injection rate, injection time, and number of cycles. Primary depletion period and soaking time are less noticeable for the well performance in the selected case. Considering the effect of confinement and molecular diffusion leads to the increase in the well performance during the CH4 injection process. This work, for the first time, evaluates the nanopore effects and molecular diffusion on the CH4 injection. It provides an efficient numerical method to predict the well production in the EOR process. Additionally, it presents useful insights into the prediction of cyclic CH4 injection effectiveness and helps operators to optimize the EOR process in the shale reservoirs.