Long‐term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low‐intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE‐LTICv cells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk‐pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted. What's new? Tumor Treating Fields (TTFields), in which tumor cell division is disrupted by exposure to alternating electric fields, are a promising therapeutic strategy against cancer. In this study, TTFields are shown to enhance the efficacy of paclitaxel in ovarian cancer, both in vitro and in vivo. The feasibility of effectively delivering TTFields across a large nonuniform volume, encompassing ovaries and potential metastatic sites, is demonstrated via electric field measurements in mice and through finite‐element mesh simulations. The results have given impetus to an open‐label pilot investigation of TTFields administered in combination with paclitaxel in patients with recurrent ovarian cancer.