© 2022 by the authors.Microwave hyperthermia (MH) requires the effective calibration of antenna excitations for the selective focusing of the microwave energy on the target region, with a nominal effect on the surrounding tissue. To this end, many different antenna calibration methods, such as optimization techniques and look-up tables, have been proposed in the literature. These optimization procedures, however, do not consider the whole nature of the electric field, which is a complex vector field; instead, it is simplified to a real and scalar field component. Furthermore, most of the approaches in the literature are system-specific, limiting the applicability of the proposed methods to specific configurations. In this paper, we propose an antenna excitation optimization scheme applicable to a variety of configurations and present the results of a convolutional neural network (CNN)-based approach for two different configurations. The data set for CNN training is collected by superposing the information obtained from individual antenna elements. The results of the CNN models outperform the look-up table results. The proposed approach is promising, as the phase-only optimization and phase–power-combined optimization show a 27% and 4% lower hotspot-to-target energy ratio, respectively, than the look-up table results for the linear MH applicator. The proposed deep-learning-based optimization technique can be utilized as a protocol to be applied on any MH applicator for the optimization of the antenna excitations, as well as for a comparison of MH applicators.