The opioid crisis in the United States has been defined by waves of drug- and locality-specific Opioid use-Related Epidemics (OREs) of overdose and bloodborne infections, among a range of health harms. The ability to identify localities at risk of such OREs, and better yet, to predict which ones will experience them, holds the potential to mitigate further morbidity and mortality. This narrative review was conducted to identify and describe quantitative approaches aimed at the “risk assessment,” “detection” or “prediction” of OREs in the United States. We implemented a PubMed search composed of the: (1) objective (eg, prediction), (2) epidemiologic outcome (eg, outbreak), (3) underlying cause (ie, opioid use), (4) health outcome (eg, overdose, HIV), (5) location (ie, US). In total, 46 studies were included, and the following information extracted: discipline, objective, health outcome, drug/substance type, geographic region/unit of analysis, and data sources. Studies identified relied on clinical, epidemiological, behavioral and drug markets surveillance and applied a range of methods including statistical regression, geospatial analyses, dynamic modeling, phylogenetic analyses and machine learning. Studies for the prediction of overdose mortality at national/state/county and zip code level are rapidly emerging. Geospatial methods are increasingly used to identify hotspots of opioid use and overdose. In the context of infectious disease OREs, routine genetic sequencing of patient samples to identify growing transmission clusters via phylogenetic methods could increase early detection capacity. A coordinated implementation of multiple, complementary approaches would increase our ability to successfully anticipate outbreak risk and respond preemptively. We present a multi-disciplinary framework for the prediction of OREs in the US and reflect on challenges research teams will face in implementing such strategies along with good practices.