Although the opioid epidemic and fentanyl crisis are nationwide problems of immense proportions, calming the storm raging across the isolating geo-economic framework of Appalachia demonstrates the need for courageous, culturally effective programs that have the power to address and overcome the grave situation of addiction in this region. In the Appalachian region, unjust social structures are embedded in the communities' socio-economic conditions. As this reality poses even greater barriers to addressing the opioid epidemic in these communities, the restoration of social relationships within a community becomes vital to the development of a broader approach to social functioning and human flourishing. Faith traditions and faith communities can play an important role in helping to establish and support such social cohesion through attention to the individual, social, and spiritual needs of the community. This essay explores the complex problem of the opioid epidemic compounded by the fentanyl crisis. It considers the importance of public health research within the regional geo-economic framework of Appalachia to (a) inform policies that improve health inequities and promote social cohesion, (b) develop social solutions with a spiritual dimension, and (c) reveal remedies capable of informing moral norms in support of building a more just society. Reflecting on the virtue of solidarity, this essay also highlights the witness of the Catholic Church's response to the suffering experienced within the communities and the societies within the Appalachian mountains. While there may be considerable interest in viewing this article as a research document, foundationally, this essay utilizes a literary narrative approach through a Catholic lens to inform ethical deliberations, reasoning, and practice while supporting ethical reflection and consideration of the responses raised. Further, the reader is strongly encouraged to reference the comprehensive footnote system provided for extension and verification of the data presented.