This research focuses on seismic resistance systems and design strategies for highway bridges, including base isolation, energy dissipation devices (e.g., lead-rubber bearings (LRB) and magnetorheological (MR) dampers), and hybrid approaches (e.g., elastomeric bearings with dampers). It explores advanced strategies such as elastic foundations with elastic superstructures and the integration of structural design methods to maintain elasticity during design-level earthquakes. The motivation for this study arises from the urgent need to enhance bridge resilience in seismically active regions, driven by high earthquake mortality rates and the inadequacy of modern standards, particularly for bridges with limited energy dissipation capacity. A mixed-methods approach combines 3D finite element modeling of various bridge typologies under seismic loads (magnitudes 7.0–9.0), dynamic time-history analysis in Midas Civil, parametric evaluation of 20 international case studies (e.g., San Francisco-Oakland Bridge), and cost-benefit assessments of modular construction based on FHWA datasets. The results indicate that base isolation techniques can reduce peak accelerations by 35–60% (span-dependent) and repair costs by 25–35% for small/medium spans. Hybrid systems increased energy dissipation by 70% (damper-dependent), modular construction methods can reduce construction time by 35–50%, and MR dampers decreased vibration amplitudes by 30–50%. The study concludes that enhancing seismic resilience requires integrated strategies that combine various design approaches and innovative technologies with monitoring aided by artificial intelligence. Recommendations include refining design standards and incorporating advanced monitoring systems to improve the seismic performance of highway bridges.