The seismic performance of caisson and pier bridge systems significantly depends on the complex interaction between the foundation, soil, and superstructure. This study investigates the influence of interface non-linearity on the seismic response of such systems using a finite element approach under strong earthquake excitation. The soil-foundation-pier-deck system is modeled to capture the realistic behavior at the interface between the soil and the foundation elements. The results are compared with a perfectly bonded interface approach. The findings reveal that neglecting interface non-linearity can lead to significant underestimation of pier rotation and overestimation of structural demands, potentially resulting in uneconomical designs and compromised structural integrity. Additionally, post-earthquake permanent settlements and rotation are more pronounced when considering interface non-linearity. The study also explores the use of both non-linear and viscoelastic soil models. Therefore, this study emphasizes the need to incorporate interface and soil non-linearity for economical design practices and to ensure structural resilience under earthquake loads.