An optimization of the excitation–measurement configuration is proposed for the characterization of damage in PZT-4 piezoelectric plates, from a numerical point of view. To perform such an optimization, a numerical method to determine the location and extent of defects in piezoelectric plates is developed by combining the solution of an identification inverse problem, using genetic algorithms and gradient-based methods to minimize a cost functional, and using an optimized finite element code and meshing algorithm. In addition, a semianalytical estimate of the probability of detection is developed and validated, which provides a flexible criterion to optimize the experimental design. The experimental setup is optimized upon several criteria: maximizing the probability of detection against noise effects, ensuring robust search algorithm convergence and increasing the sensitivity to the presence of the defect. The measurement of voltage ϕ is concluded to provide the highest identifiability, combined with an excitation of the specimen by a mechanical traction transverse to the polarization direction. Sufficient accuracy is predicted for the damage location and sizing under realistic noise levels.