Abstract Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.