Global population aging and increased chronic stress due to numerous mass disasters including those related to pandemics, climate change, war, displacement, and political unrest all challenge our collective resilience, with a growing burden of late-life neuropsychiatric and neurodegenerative disorders placing unprecedented demands on health and social systems worldwide. With these considerations in mind, understanding and promoting brain health is becoming a priority for the prevention of neuropsychiatric disorders across the lifespan. Brain health represents a dynamic balance of neural, cognitive, and emotional processes that determine resilience to neuropsychiatric illness. In later life, this balance becomes particularly critical as neurobiological and psychosocial stressors converge to shape trajectories of neuropsychiatric and neurodegenerative disorders. This review synthesizes current evidence on the determinants of brain health in aging, emphasizing resilience as a modifiable pathway linking neuropsychiatric illness risk and prevention. We integrate insights from neuroscience, lifestyle medicine, geroscience, and social determinants of health to emphasize the value of a whole-person, life-course approach. Particular attention is given to the interplay between stress physiology, interoceptive regulation, emotional resilience, and cognitive and brain reserve across the aging continuum. Emerging frameworks including brain clocks, precision biomarkers, digital phenotyping, and artificial intelligence, are considered as tools for risk stratification, early detection, and personalized intervention. By linking resilience mechanisms to measurable biological indices, we argue for the integration of neurobiological, psychological, behavioral, and sociocultural domains to inform next-generation strategies in neuropsychopharmacology, prevention science, and the promotion of healthy brain aging.