Emotion studies show that ventromedial prefrontal cortex (vmPFC) plays a critical role in negative affect evaluation. Here we investigated two questions: Does the neural sensitivity to threat of bodily harm in vmPFC alter as anxiety levels increase? If the neural sensitivity to threat in vmPFC reflects a kind of general emotional processing, does it predict reward processing? To address these questions, we first recorded participants’ self-reported anxiety. In an investigation of neural responses in vmPFC (Session 1), we measured brain activity (fMRI) associated with the anticipation of threat, using a sphere based ROI approach. In a behavioral experiment (Session 2), participants’ reward processing efficiency was evaluated when they performed a visual discrimination task in which they had the opportunity to earn cash rewards. We found that across participants, there were tightly coupled associations between signal changes in the vmPFC and self-reported state anxiety. Specifically, participants who showed more activation in vmPFC to threat also exhibited greater behavioral efficiency in reward processing. Path analysis revealed a closely interconnected network of vmPFC (cortical) and VS (ventral striatum, subcortical) which predicted reward processing. Therefore, in addition to negative affect evaluation, neural sensitivity in vmPFC correlated with both anxiety and reward-related metrics. These results support an emerging model in which the vmPFC functions to defend the organism from acute stress and facilitate reward processes.