Abstract Background: Tumor Treating Fields (TTFields) therapy is a noninvasive, anticancer treatment delivered by two pairs of arrays placed on the skin surrounding the tumor location. Based on efficacy and safety data from phase 3 global clinical studies, TTFields therapy is FDA-approved and CE marked for treatment of glioblastoma (GBM), the most common malignant brain tumor. In vivo studies of TTFields in GBM models, which are mostly based on mice, are complicated by the relatively small size of the mouse head and corresponding limited surface area to apply the arrays. This challenge has thus far limited in vivo research on TTFields treatment in GBM. Materials and Methods: To identify a method for efficient delivery of TTFields to the mouse brain, we examined the ability of different array layouts to accommodate the geometries of the mouse head while minimally impacting head movement, taking into account that it may not be feasible to place two pairs of arrays on the head. The properties of different adhesive tapes, specifically their ability to attach to the skin, was also investigated. Finally, the ability of array layouts to deliver therapeutic intensities to the desired region was validated using simulations and direct electric field measurements. Results: Assessments showed an optimal layout consisted of arrays such that one of the pair was on the mouse head, and the other on the mouse torso; and the arrays for placement on the head divided into two smaller disks, A thin, transparent adhesive tape was identified that allowed the arrays to be securely attached to the skin, but was easily removed without leaving residues. Validation studies using simulations demonstrated that the array layout met the minimum treatment requirements (field intensity ≥1 V/cm RMS; current ≥50 mA), and facilitated TTFields usage for ≥75% of each day. Conclusions: These data show that TTFields treatment can be effectively delivered to the heads of mice by utilizing carefully designed arrays. Our newly developed mouse head arrays are a flexible construct, that adheres strongly to the skin, and enables efficient electric field delivery to the mouse brain. These improvements in the delivery of TTFields treatment to mice will facilitate research of TTFields as a therapy for GBM. Citation Format: Sewar Zbidat, Roni Blatt, Mariell Sellevoll, Martin Gabay, Inbar Schlachet, Shay Cahal, Shiri Davidi, Itai Tzchori, Amal El-Mabhouh, Adi Haber, Moshe Giladi, Yoram Palti. Designing arrays for the mouse head to facilitate in vivo studies of Tumor Treating Fields (TTFields) treatment of glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B032.