In order to reduce seismic responses of a structure, additional dampers and vibration control devices are generally considered. Usually, control performance of additional devices are investigated for optimal design without variation of characteristics of a structure. In this study, multi-objective integrated optimization of structure-smart control device is conducted and possibility of reduction of structural resources of a building structure with smart top-story isolation system has been investigated. To this end, 20-story example building structure was selected and an MR damper and low damping elastomeric bearings were used to compose a smart base isolation system. Artificial earthquakes generated based on design spectrum of low-to-moderate seismicity regions are used for structural analyses. Based on numerical simulation results, it has been shown that a smart top-story isolation system can effectively reduce both structural responses and isolation story drifts of the building structure in low-to-moderate seismicity regions. The integrated optimal design method proposed in this study can provide various optimal designs that presents good control performance by appropriately reducing the amount of structural material and damping device.