In this study friction pendulum system (FPS) bearings and precast-prestressed pile (PPP) isolators are considered as base isolation devices for a Chilean confined masonry house. The house is numerically modeled using a multiple degree-of-freedom approach that is calibrated with experimental data. Dynamic behavior of the FPS and PPP isolators is simulated using analytical formulations based on laboratory testing. Optimization of the isolators is performed using an earthquake that is generated to match the design spectrum for the house based on Chilean seismic code. A non-dominated sorting genetic algorithm (NSGA-II) is applied to carry out the optimization. Seismic response of the base-isolated structure subjected to a suite of ground motions is compared to the performance of the traditionallyconstructed structure by means of several performance indices (PIs). Numerical simulations indicate that the PPP isolation system is more effective in reducing the base and structural shear, interstory drift, and floor acceleration of the structure than the FPS isolation system, although both systems result in substantial reductions of the response.