Fentanyl’s Deadly Footprint: A New Framework for Predicting Overdose Hotspots

Illicitly manufactured fentanyl has become a major driver of fatal drug overdoses in the United States, with annual mortality approaching six figures. Spatial analyses consistently demonstrate that the overdose burden clusters within structurally vulnerable micro-areas rather than distributing uniformly across regions. A narrative review of US studies (2010-2025) synthesized evidence from mortality, emergency department, emergency medical services, wastewater, social media, and related data streams that examined small-area patterns or the prediction of fentanyl or synthetic opioid overdose. Evidence shows a strongly clustered fentanyl burden, with small-area mapping identifying persistent hotspots and Bayesian forecasting and nowcasting models providing short-horizon predictions. Emerging wastewater and social media indicators offer additional early warning capacity, especially where routine surveillance is sparse. However, external validation, calibration reporting, uncertainty characterization, and equity-sensitive performance metrics are uncommon. This review organizes these strands into a three-tier framework--mortality-only, EMS and emergency department, and multi-stream environments--that links mapping, forecasting, and spike detection to operational response while embedding explicit equity and governance safeguards.