Objectives Distinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks. Design A cross-sectional and retrospective observational study. Setting A population-based French cohort (CONSTANCES). Participants 130 197 adults enrolled between 2012 and 2021 without missing values. Primary outcome measures The associations of social position, work environment and unemployment exposure with the prevalence of cardiovascular events and cancers simultaneously tested using logistic regression models adjusting for common risk factors. Results While social position, work environment and unemployment exposure are strongly interrelated with each other, they are not linked to the same cardiovascular and cancer outcomes. Low social position and long unemployment duration are significantly associated with an increased prevalence of angina pectoris, myocardial infarction and peripheral arterial disease (OR=1.22 to 1.90, p<0.04 to p<0.0001) but not of stroke. In contrast, a bad work environment is associated with an increased prevalence of stroke (OR=1.29, p<0.01) but not of angina pectoris, myocardial infarction and peripheral arterial disease. Low social position is associated with an increased prevalence of cervical and lung cancers (OR=1.73 and 1.95, p<0.002 and p<0.03) and a decreased prevalence of skin cancer (OR=0.70, p<0.0001) while a bad work environment is associated with an increased prevalence of breast, skin, prostate and colon cancers (OR=1.31 to 2.91, p<0.0002 to p<0.0001). Unemployment exposure is not associated with the prevalence of any type of cancers. Conclusions Social position, work environment and unemployment are associated with distinct cardiovascular and cancerous diseases that could add up during lifetime, they should therefore be considered all together in any preventive strategy.