This work aims to develop a reasonable pre-camber design method for long-span cable-stayed bridges by investigating the high-speed train-bridge interaction under complex environmental loads, including ambient temperature, concrete creep, and concrete shrinkage (CCCS). First, an integrated dynamic model of the train-track-cable stayed bridge system (TTCSBS) is established using multibody dynamics and finite element theory and validated through field test. Then, the temperature change features at several key positions on the long-span bridge are investigated using long-term monitoring data. Temperature-induced bridge deformation is calculated by applying the established bridge finite element model (FEM) and compared with test results. CCCS-induced bridge deformation is determined through numerical calculations that consider the bridge's structural and material properties. On this basis, the effects of bridge deformation caused by environmental loads on vehicle-bridge dynamic interaction are investigated in detail, and a new bridge pre-camber design method is proposed to counteract the effects of both environmental and train dynamic loads. Results indicate that the proposed model's simulations align well with field test data. The long-span bridge deformation induced by the environmental loads intensifies the dynamic responses of a running vehicle, particularly the wheel-rail vertical force and car-body vertical vibration. However, it has slight influence on train-induced bridge vibration. The proposed pre-camber design method for long-span bridges, which accounts for long-term environmental load action, effectively ensures good vehicle service performance. The research results could provide useful guidance for the design of long-span bridge systems.