The emerging paradigms of Beyond-5G, 6G and Super-IoT will demand for Radio Frequency (RF) passive components with pronounced performance, and RF-MEMS technology, i.e. Microsystem-based RF passives, is a good candidate to meet such a challenge. As known, RF-MEMS have a complex behavior, that crosses different physical domains (mechanical; electrical; electromagnetic), making the whole design optimization and trimming phases particularly articulated and time consuming. In this work, we propose a novel design optimization approach based on the Response Surface Method (RSM) statistical methodology, focusing the attention on a class of RF-MEMS-based programmable step power attenuators. The proposed method is validated both against physical simulations, performed with Finite Element Method (FEM) commercial software tools, as well as experimental measurements of physical devices. The case study here discussed features 3 DoFs (Degrees of Freedom), comprising both geometrical and material parameters, and aims at optimizing the RF performance of the MEMS attenuator in terms of attenuation (S21 Scattering parameter) and reflection (VSWR – Voltage Standing Wave Ratio). When validate, the proposed RSM-based method allows avoiding physical FEM simulations, thus making the design optimization considerably faster and less complex, both in terms of time and computational load.