Socioeconomic status (SES)-related health disparities persist for numerous chronic diseases, with lower-SES individuals exhibiting greater risk of morbidity and mortality compared to their higher-SES counterparts. One likely contributor is disparities in health messaging efforts, which are currently less effective for motivating health behavior change among those lower in SES. Drawing on communication neuroscience and social neuroscience research, we describe a conceptual framework to improve health messaging effectiveness in lower SES communities. The framework is based on evidence that health-message-induced activity in the ventral striatum (VS) and subdivisions of the medial pre-frontal cortex (MPFC) predicts behavior change. Additionally, we draw from social neuroscience work showing that activity in these regions during valuation and the processing of self-related vs. social information, differs as a function of SES. Bringing together these previously disparate lines of work, we argue that health messages emphasizing the benefits to close others (vs. the self) of engaging in behavior change will be more effective among lower SES individuals. We also outline a research agenda based on our framework. Ultimately, we hope that this framework utilizing a “brain-as-predictor” approach generates novel insights about the neural underpinnings of message-induced behavior change among lower SES individuals, and helps to close the gap in SES-based health disparities by harnessing the power of neuroimaging.