This paper formulates a response prediction formula based on complex modal superposition and frequency response functions of single-degree-of-freedom systems for both storey drift and floor acceleration of a mid-storey-isolated building under the assumption of white noise input. This study verifies that the proposed formula can estimate the seismic response of a building accurately, even if a system includes the overdamped mode, by comparing the same with the results of a time-history analysis. To support the structural design of a midstorey-isolated building, the proposed formula is applied to an optimal design problem, which considers the objective function of acceleration response in a superstructure and constraints on storey drifts. A genetic algorithm is employed to obtain the optimal stiffness distribution and damping coefficient of the isolation layer. This study confirms that the acceleration response of the optimal design is successfully reduced, with other responses remaining within acceptable ranges.