In this paper, we present an efficient framework for optimization of MEMS resonators based on model order reduction and memoization to significantly speed-up computations 40 x). Owing to their technological importance and numerous applications, unreleased CMOS resonant body transistors (RBTs) are considered. Their intricate structure requires computationally intensive finite element method (FEM) frequency domain simulations, which hinders their optimization. In this work, numerical optimization combined with a physics-based phononic crystal (PnC) waveguide design enables the realization of unreleased CMOS-RBTs with record breaking performance. The optimized RBTs have been fabricated in IBM 32nm SOI technology, demonstrating a quality factor Q ∼ 11,620 at 3.252 GHz for an f · Q ∼ 3.8 × 1013.