Introduction: university students experience multiple stressors impacting mental health. Identifying protective factors and risk factors is key to fostering psychological flourishing. Selected variables reflect evidence-based determinants of flourishing in emerging adults. Purpose: this study examines whether self-esteem and basic psychological need satisfaction predict well-being beyond depressive symptoms, loneliness, and personality dysfunction. Method: hierarchical multiple regression was performed on cases with complete data (N = 1.319), using psychological well-being (MHC-SF) as the dependent variable. Results: step 1 explained 3.4% of variance in well-being (p < .001). Risk factors accounted for an additional 43.4% (R² = .467, p < .001). Adding protective factors increased explained variance to 55.3% (ΔR² = .086, p < .001). In the final model, higher self-esteem (β = .36, p < .001) and need satisfaction (β = .11, p < .001) predicted greater flourishing, whereas depressive symptoms (β = −.18, p < .001), loneliness (β = −.21, p < .001), and personality dysfunction (β = −.18, p < .001) predicted lower well-being. All VIF values < 2. Conclusions: beyond psychopathology and personality impairment, self-esteem and fulfillment of psychological needs uniquely contribute to flourishing among university students. Interventions enhance autonomy, competence, and relatedness, as well as self-worth promotion, and may substantially strengthen well-being within the Me.Mo program.