Research indicates that core dimensions of psychological well-being can be cultivated through intentional mental training. Despite growing research in this area and an increasing number of interventions designed to improve psychological well-being, the field lacks a unifying framework that clarifies the dimensions of human flourishing that can be cultivated. Here, we integrate evidence from well-being research, cognitive and affective neuroscience, and clinical psychology to highlight four core dimensions of well-being—awareness, connection, insight, and purpose. We discuss the importance of each dimension for psychological well-being, identify mechanisms that underlie their cultivation, and present evidence of their neural and psychological plasticity. This synthesis highlights key insights, as well as important gaps, in the scientific understanding of well-being and how it may be cultivated, thus highlighting future research directions.