Background: Temporal interference (TI) electrical stimulation is a novel neuromodulation method that can target deep brain structures to enhance the impact of behavioral techniques. We tested the feasibility of TI targeting the ventral striatum (VS) during an emotion regulation practice (breath-focused mindfulness meditation). To assess target engagement, we used electroencephalography (EEG) to measure amplitude of the reward positivity (RewP), an event-related potential (ERP) associated with cortico-striatal reward circuitry. Methods: Nineteen healthy adults (age range: 18-36 years) received an MRI scan and two stimulation sessions during meditation: one active 8 Hz TI stimulation and one 0 Hz sham TI. Before and after meditation, they completed a reward task during EEG recording. Results: A significant time by stimulation effect was observed with the RewP win-loss difference (p < .001; eta(2)(p) = .61), but not with an attentional control-related ERP, the Cue-N200 (p = .93). Active TI, but not sham, led to a RewP increase from pre- to post-stimulation, with evidence of a sustained RewP amplitude increase at visit 2 in participants who received active TI at visit 1 (p < .001). This effect was driven by a win trial increase. Decreased negative emotionality (anxiety) was observed for active TI; emotion changes corresponded with increased RewP amplitude to win trials for only active TI. Conclusion: Findings show support for TI targeting VS in conjunction with meditation to elicit self-reported and neural change in emotion regulation and reward processing. Although replication is warranted, our data indicates relative precision and short-term continued effects of TI on the VS and reward-related functioning.