The opioid crisis presents substantial challenges to public health in New England's rural states, where access to pharmacotherapy for opioid use disorder (OUD), harm reduction, HIV and hepatitis C virus (HCV) services vary widely. We present an approach to characterizing the epidemiology, policy and resource environment for OUD and its consequences, with a focus on eleven rural counties in Massachusetts, New Hampshire and Vermont between 2014 and 2018. We developed health policy summaries and logic models to facilitate comparison of opioid epidemic-related polices across the three states that could influence the risk environment and access to services. We assessed sociodemographic factors, rates of overdose and infectious complications tied to OUD, and drive-time access to prevention and treatment resources. We developed GIS maps and conducted spatial analyses to assess the opioid crisis landscape. Through collaborative research, we assessed the potential impact of available resources to address the opioid crisis in rural New England. Vermont's comprehensive set of policies and practices for drug treatment and harm reduction appeared to be associated with the lowest fatal overdose rates. Franklin County, Massachusetts had good access to naloxone, drug treatment and SSPs, but relatively high overdose and HIV rates. New Hampshire had high proportions of uninsured community members, the highest overdose rates, no HCV surveillance data, and no local access to SSPs. This combination of factors appeared to place PWID in rural New Hampshire at elevated risk. Study results facilitated the development of vulnerability indicators, identification of locales for subsequent data collection, and public health interventions.