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Using a sample of over 1,000 workers from the American Working Conditions Survey (AWCS), this study examines the relationship between work–family conflict (both work-to-family and family-to-work conflict) and three aspects of well-being: self-rated health, life satisfaction, and psychological distress. Moreover, it tests whether these associations differ by levels of extrinsic and intrinsic job resources (managerial support and meaningful work, respectively). The results show that higher levels of work–family conflict (in both directions) are associated with lower self-rated health and life satisfaction, as well as with higher psychological distress. The study also finds evidence for the moderating effects of both meaningful work and managerial support. Specifically, managerial support moderates the positive association between work-to-family (and family-to-work) conflict and psychological distress, such that the relationship is weaker for those with higher managerial support. Similarly, meaningful work moderates the associations between work-to-family (and family-to-work) conflict and both psychological distress and life satisfaction, with these relationships being less pronounced for workers who report higher levels of meaningful work. There is less evidence, however, for the protective role of meaningful work on self-rated health. Notably, meaningful work moderates the negative association between work-to-family conflict and self-rated health, but not that for family-to-work conflict. Overall, this analysis provides stronger support for the moderating effects of intrinsic rewards (compared to extrinsic rewards), particularly on psychological distress, and it highlights key workplace policy implications for improving employee well-being.