BACKGROUND AND OBJECTIVES: The Child Opportunity Index (ChOI) is a publicly available surveillance tool that incorporates traditional and novel attributes of neighborhood conditions that may promote or inhibit healthy child development. The extent to which ChOI relates to individual-level cardiometabolic risk remains unclear. METHODS: We geocoded residential addresses obtained from 743 participants in midchildhood (mean age 7.9 years) in Project Viva, a prebirth cohort from eastern Massachusetts, and linked each location with census tract-level ChOI data. We measured adiposity and cardiometabolic outcomes in midchildhood and early adolescence (mean age 13.1 years) and analyzed their associations with neighborhood-level ChOI in midchildhood using mixed-effects models, adjusting for individual and family sociodemographics. RESULTS: On the basis of nationwide distributions of ChOI, 11.2% (n = 83) of children resided in areas of very low overall opportunity (ChOI score <20 U) and 55.3% (n = 411) resided in areas of very high (ChOI score ≥80 U) overall opportunity. Children who resided in areas with higher overall opportunity in midchildhood had persistently lower levels of C-reactive protein from midchildhood to early adolescence (per 25-U increase in ChOI score: β = .14 mg/L; 95% confidence interval, .28 to .00). Additionally, certain ChOI indicators, such as greater number of high-quality childhood education centers, greater access to healthy food, and greater proximity to employment in midchildhood, were associated with persistently lower adiposity, C-reactive protein levels, insulin resistance, and metabolic risk z scores from midchildhood to early adolescence. CONCLUSIONS: Our findings suggest more favorable neighborhood opportunities in midchildhood predict better cardiometabolic health from midchildhood to early adolescence.