Ongoing assessments by climate scientists, including a recent report from the United Nations' Intergovernmental Panel on Climate Change, punctuate the pronounced effect that climate change is poised to have in the near future on the health and well-being of humans-particularly those with low socioeconomic status-throughout the world. To this end, to date, very limited scholarly attention has been placed on the effects that climate change may have on people who use drugs (PWUDs), in particular those with opioid use disorder, and assessed their structural and social determinants of climate change vulnerability. Since COVID-19, which has key lessons to offer on climate change's potential effects on PWUDs, the opioid epidemic has been rapidly accelerating in terms of its socioeconomic, racial, and geographic reach. The opioid epidemic has been further deepened by increasing fentanyl contamination and co-use with stimulants such as methamphetamine and (crack) cocaine, spurring a heavy increase in overdose deaths. These trends highlight a looming confrontation between the world's complex overdose crisis and its equally intensifying climate emergency. This piece contextualizes the specter of harms that climate change is likely to cultivate against PWUDs and offers strategies for mitigation.