An extensive epidemiological literature indicates that increased exposure to tobacco retail outlets (TROs) places never smokers at greater risk for smoking uptake and current smokers at greater risk for increased consumption and smoking relapse. Yet research into the mechanisms underlying this effect has been limited. This preliminary study represents the first effort to examine the neurobiological consequences of exposure to personally relevant TROs among both smokers (n = 17) and nonsmokers (n = 17). Individuals carried a global positioning system (GPS) tracker for 2 weeks. Traces were used to identify TROs and control outlets that fell inside and outside their ideographically defined activity space. Participants underwent functional MRI (fMRI) scanning during which they were presented with images of these storefronts, along with similar store images from a different county and rated their familiarity with these stores. The main effect of activity space was additive with a Smoking status × Store type interaction, resulting in smokers exhibiting greater neural activation to TROs falling inside activity space within the parahippocampus, precuneus, medial prefrontal cortex, and dorsal anterior insula. A similar pattern was observed for familiarity ratings. Together, these preliminary findings suggest that the otherwise distinct neural systems involved in self-orientation/self-relevance and smoking motivation may act in concert and underlie TRO influence on smoking behavior. This study also offers a novel methodological framework for evaluating the influence of community features on neural activity that can be readily adapted to study other health behaviors.