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Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether the effects of brain stimulation can be enhanced by simultaneously targeting a region and its network, identified with resting state functional connectivity MRI. Fifteen healthy participants received two types of transcranial direct current stimulation (tDCS): a traditional two-electrode montage targeting a single brain region (left primary motor cortex [M1]) and a novel eight-electrode montage targeting this region and its associated resting state network. As a control, 8 participants also received multifocal tDCS mismatched to this network. Network-targeted tDCS more than doubled the increase in left M1 excitability over time compared to traditional tDCS and the multifocal control. Modeling studies suggest these results are unlikely to be due to tDCS effects on left M1 itself, however it is impossible to completely exclude this possibility. It also remains unclear whether multifocal tDCS targeting a network selectively modulates this network and which regions within the network are most responsible for observed effects. Despite these limitations, network-targeted tDCS appears to be a promising approach for enhancing tDCS effects beyond traditional stimulation targeting a single brain region. Future work is needed to test whether these results extend to other resting state networks and enhance behavioral or therapeutic effects. •Resting state functional connectivity can guide multifocal tDCS.•tDCS effects can be enhanced with network-targeted stimulation.•Multifocal tDCS mismatched to a network fails to produce similar effects.