This article synthesizes foundational knowledge from multiple scientific disciplines regarding how humans develop in context. Major constructs that define human development are integrated into a developmental system framework, this includes--epigenetics, neural malleability and plasticity, integrated complex skill development and learning, human variability, relationships and attachment, self-regulation, science of learning, and dynamics of stress, adversity and resilience. Specific attention is given to relational patterns, attunement, cognitive flexibility, executive function, working memory, sociocultural context, constructive development, self-organization, dynamic skill development, neural integration, relational pattern making, and adverse childhood experiences. A companion article focuses on individual-context relations, including the role of human relationships as key drivers of development, how social and cultural contexts support and/or undermine individual development, and the dynamic, idiographic developmental pathways that result from mutually influential individual-context relations across the life span. An understanding of the holistic, self-constructive character of development and interconnectedness between individuals and their physical, social, and cultural contexts offers a transformational opportunity to study and influence the children's trajectories. Woven throughout is the convergence of the science of learning -- constructive developmental web, foundational skills, mindsets (sense of belonging, self-efficacy, and growth mindset), prior knowledge and experience, motivational systems (intrinsic motivation, achievement motivation, and the Belief-Control-Expectancy Framework), metacognition, conditions for learning , cultural responsiveness and competence, and instructional and curricular design- and its importance in supporting in integrative framework for children's development. This scientific understanding of development opens pathways for new, creative approaches that have the potential to solve seemingly intractable learning and social problems.