Significant technological advances in sensing and communication promote the use of large sensor networks to monitor structural systems, identify damages, and quantify damage levels. Prognostics and health management (PHM) technique has been developed and applied for a variety of safety-critical engineering structures, given the critical needs of the structure health state awareness. The PHM performance highly relies on real-time sensory signals which convey the structural health relevant information. Designing an optimal structural sensor network (SN) with high detectability is thus of great importance to the PHM performance. This paper proposes a generic SN design framework using a detectability measure while accounting for uncertainties in material properties and geometric tolerances. Detectability is defined to quantify the performance of a given SN. Then, detectability analysis will be developed based on structural simulations and health state classification. Finally, the generic SN design framework can be formulated as a mixed integer nonlinear programming (MINLP) using the detectability measure and genetic algorithms (GAs) will be employed to solve the SN design optimization problem. A power transformer study will be used to demonstrate the feasibility of the proposed generic SN design methodology.