The promotion of mental health, and the prevention of psychological disease, have come increasingly into focus in recent years. This is especially true for adolescents and young adults, who due to their stages in development face unique challenges in achieving good mental health. Among these challenges is the formation of major psychological constructs such as self-esteem and personality. The interaction between these variables and others such as subjective well-being and internalizing problems may help explain how a person’s mental health is determined. 150 college students answered self-report questionnaires on self-esteem, the Big Five traits, subjective well-being, and internalizing problems. The results showed that self-esteem played a mediating role between subjective well-being and internalizing problems. One Big Five trait, neuroticism, was found to play a moderating role in this mediation relationship between self-esteem and internalizing problems. Our findings suggest that a person’s psychological development, influenced by a complex mix of cognitive, behavioral, and emotional forces, plays a unique role in the dynamic between mental wellness and mental illness. The broader impact of the findings is to develop mental health treatment plans for emerging adults to promote positive development.