Background: Over the past two decades, some countries have experienced high and/or rising rates of drug-related deaths (DRDs), increasing inequalities, welfare state retrenchment, and reduced well-being. Objective. This study uses a comparative approach to explore and discuss the influence of social and structural determinants of health (SDH) on DRDs and implications for drug policy. Methods: Open data is used to compare SDH and DRD in Sweden, the United Kingdom and Ireland, which according to EUDA consistently rank among the countries with the highest DRD in Europe and share both similarities and differences in how social issues are addressed. Section one uses Global Burden of Diseases and EUDA data to chart DRD over the past 20 years. The second section compares drug policy changes over time. Section three examines social policy developments in terms of SDH (e.g. social indicators of inequality, welfare state retrenchment, labour market restructuring, area deprivation, and austerity) by using databases like the UN SDG Indicators and Social Policy Indicators (SPIN)). The analysis is informed by a review of theoretical frameworks, including the key distinction between macro and meso levels, and principles and methods of comparative research. Results: Similarities and differences were identified on a range of variables, e.g. DRD, drug policy goals, social expenditures and protection (adequacy, eligibility). Implications: Drug policy may differ from and follow different paths than other social/public health policies. DRD can be influenced by both, but the significance of each varies by overall contextual factors, including access to effective services.