As challenges to child well-being through economic disadvantage, family disruption, and migration or displacement escalate world wide, the need for cross-culturally robust understanding of childhood adversity proportionately increases. Toward this end, developmental risk was assessed in four contrasting groups of 107 Nepali children ages 10–14 years that represent distinctive, common conditions in which contemporary children grow up. Relative cumulative burden (allostatic load) indexed by multiple dimensions of physical and psychosocial stress was ascertained among homeless street boys and three family-based groups, from poor urban squatter settlements, urban middle class, and a remote rural village. Biomarkers of stress and vulnerability to stress included growth status, salivary cortisol, antibodies to Epstein–Barr virus, acute phase inflammatory responses (alpha1-antichymotrypsin), and cardiovascular fitness and reactivity (flex heart rate and pressor response). Individual biomarkers of risk and allostatic load differed markedly among groups, were highest in villagers, and varied by components of allostatic load. Such data suggest a need for critical appraisal of homelessness and migration as a risk factor to youth, given prevailing local conditions such as rural poverty, and represents the only multidimensional study of childhood allostatic load and developmental risk in non-Western settings.