An effective CAD methodology to perform efficient EM-based design optimization of microwave circuits using surrogate models based on polynomial functional interpolants is described. This surrogate-driven design procedure is especially suitable for cases where a continuous coarse model is not available The corresponding surrogate models are formulated as low-order functions of the design available. variables, and are used to interpolate highly accurate electromagnetic responses in a region of interest around a selected reference design. Global optimal values for the surrogate model weighting factors are efficiently obtained in closed form, using compact formulas. Exhaustive evaluation of the generalization performance of this surrogate modeling approach is addressed. The proposed CAD methodology is illustrated using commercially available EM simulators Sonnet and CST Microwave Studio for the design optimization of several high-speed PCB interconnect structures.ITESO, A.C.