This article seeks to forge scientific connections between three overarching themes (culture, inequality, health). Although the influence of cultural context on human experience has gained notable research prominence, it has rarely embraced another large arena of science focused on the influence social hierarchies have on how well and how long people live. That literature is increasingly focused psychosocial factors, working interactively with biological and brain-based mechanisms, to account for why those with low socioeconomic standing have poorer health. Our central question is whether and how these processes might vary by cultural context. We draw on emerging findings from two parallel studies, Midlife in the U.S. and Midlife in Japan, to illustrate the cultural specificity evident in how psychosocial and neurobiological factors are linked with each other as well as how position in social hierarchies matters for psychological experience and biology. We conclude with suggestions for future multidisciplinary research seeking to understand how social hierarchies matter for people’s health, albeit in ways that may possibly differ across cultural contexts.