This threat assessment examines the evolving presence and impact of highly potent synthetic opioids, particularly the group of 2-benzylbenzimidazole opioids (the so-called ‘nitazenes’) and carfentanil, in Estonia, Latvia and Lithuania. Over the past decade, these substances have largely replaced fentanyl and heroin, leading to a high burden of drug-induced deaths and acute toxicity cases. The Baltic region is disproportionately affected by this phenomenon, with the majority of nitazenes and all carfentanil seizures in the EU taking place in these three countries. The continued adaptability of synthetic opioid markets, the challenges in implementing and scaling up harm reduction responses, and gaps in monitoring systems highlight the need for a more coordinated and sustainable approach at both the national and EU levels.