Human brain development is influenced by early-life experiences, particularly during sensitive periods, with impact on cognitive and emotional outcomes. Understanding how the timing and nature of such experiences (including adversity, trauma, and enrichment) govern their influence on brain organization is crucial for harnessing key environmental factors early in life to enhance brain development. Here we synthesize findings from human and animal studies focusing on sensitive periods and their regional and circuit specificity and highlight the challenge and power of such cross-species approaches in informing the 'next steps' to optimize cognitive and emotional health in developing children. We propose designs for neurodevelopmental optimization research programs utilizing randomized enhancement trials in early childhood to inform public health strategies on prevention and early intervention.