BackgroundTranscranial focused ultrasound (tFUS) neuromodulation has shown promise in animals but is challenging to translate to humans because of the thicker skull that heavily scatters ultrasound waves. ObjectiveWe develop and disseminate a model-based navigation (MBN) tool for acoustic dose delivery in the presence of skull aberrations that is easy to use by non-specialists. MethodsWe pre-compute acoustic beams for thousands of virtual transducer locations on the scalp of the subject under study. We use the hybrid angular spectrum solver mSOUND, which runs in ∼4 s per solve per CPU yielding pre-computation times under 1 h for scalp meshes with up to 4000 faces and a parallelization factor of 5. We combine this pre-computed set of beam solutions with optical tracking, thus allowing real-time display of the tFUS beam as the operator freely navigates the transducer around the subject’ scalp. We assess the impact of MBN versus line-of-sight targeting (LOST) positioning in simulations of 13 subjects. ResultsOur navigation tool has a display refresh rate of ∼10 Hz. In our simulations, MBN increased the acoustic dose in the thalamus and amygdala by 8–67 % compared to LOST and avoided complete target misses that affected 10–20 % of LOST cases. MBN also yielded a lower variability of the deposited dose across subjects than LOST. ConclusionsMBN may yield greater and more consistent (less variable) ultrasound dose deposition than transducer placement with line-of-sight targeting, and thus could become a helpful tool to improve the efficacy of tFUS neuromodulation.