Recent studies indicate that the structural collapse probability of large-scale seismically isolated structures under seismic actions and the effect of vertical seismic effects are usually neglected in structural analysis. The differences in the seismic design codes in different countries also lead to a challenge in assessing the structural efficiency. A numerical model is developed in this paper for investigating the behavior of an elevated large-scale transportation hub with series seismic isolation systems (SIS). The 3D finite element model considers concrete and steel stiffness degradation under reciprocating seismic actions, geometric nonlinearity and both horizonal and vertical seismic actions, which aims to provide a reliable and simplified tool to describe the seismic performance of seismically isolated structures designed by the minimum criteria of GB 50011–2010 and ASCE/SEI 7–16. Nonlinear time history analysis of six seismic waves under MCER and extremely rare strong earthquakes is carried out to study the base shear, drifts of columns and isolation bearings, structural failure, energy dissipation and vertical load effects. The results show that the structure designed according to ASCE/SEI 7 has better performance when the seismically isolated structure subjected to MCER due to additional reinforcements. When the structure is subjected to extremely rare strong earthquakes, structures designed according to GB50011 shows a higher probability of structural collapse.