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In urban areas there are frequently large and concentrated pockets of under-resourced neighborhoods. Structural equation modeling was used to investigate predictive associations between kindergarten academic, socio-behavioral, and biotic influences on third-grade academic achievement among a sample of low-SES children from urban areas. Findings validate that developmental and learning trajectories start early and are influenced by multifaceted factors. Children residing in urban poverty are at-risk for academic and developmental difficulties. Study findings established that among low-SES urban children disparities in early learning and development exist. Understanding factors that positively and negatively affect learning and development informs intervention strategies, potentially moderating gaps in these areas between socioeconomic groups. Noteworthy findings related to within-SES differences potentially impacting children’s academic trajectories are discussed.