For the response of the train-track-bridge system under extreme environment, an increasing number of studies employ co-simulation strategies for detailed modeling and calculation of the structure. However, there is a lack of research on the module connectors, which significantly impact simulation accuracy and stability. In this paper, the theoretical differences between weak, moderate, and strong coupling methods in dealing with co-simulation module interface connectors are discussed. An explicit-implicit multi-timestep co-simulation platform is established using MATLAB and OPENSEES software. Taking China's CRTS II slab ballastless track, a simply supported beam bridge, and a train as examples, a three-dimensional train-track-bridge coupling model is created. The three coupling methods are then verified and compared. Finally, two coupling methods are used to model and calculate the train-track-bridge system under earthquake. It is concluded that when calculating the train-track-bridge under earthquake, using the fastener with less damage as the co-simulation partition boundary can avoid complex nonlinear calculation. On this basis, it is feasible to use weak, moderate and strong coupling methods to deal with fastener elements. Different co-simulation software can adopt different coupling methods according to the difficulty of modeling. In the MATLAB-OPENSEES multi-timestep explicit-implicit co-simulation platform, the weak and moderate methods can achieve better calculation accuracy, and can be used to calculate the response of train-track-bridge system under earthquake.