In this paper, the centroidal Voronoi tessellation (CVT) is proposed as a design of experiments (DoE) for the nonlinear modeling of active devices. Different method’s flavors are being described, allowing to maximize the total amount of information gathered during measurements. As a case study, the CVT designs have been tested for both simulation-based experiments of nonlinear test functions, as well as for the extraction of nonlinear transfer functions of a handset radio-frequency power amplifier. The use of CVT allowed to achieve lower interpolation error, and contrary to the most popular design in microwaves, i.e., factorial DoE, the proposed tessellation can handle any arbitrary number of samples.