Comprehensive models of personality aspire to integrate the several aspects related to the study of personality in a coherent whole. One of the great research challenges in this field is to understand if and how different levels of personality analysis interrelate to promote human well-being. The aim of the present study is to explore the mediator effect of personal projects’ efficacy on the relationship between Big Five and subjective well-being (SWB) components. We conducted a cross-sectional study in which a battery of self-report questionnaires was used to assess personality and SWB in 396 teachers. Path analysis results indicated that personal projects’ efficacy fully mediated the effects of openness to experience, agreeableness and conscientiousness on life satisfaction and on negative affect. The effects of neuroticism, openness to experience, agreeableness and conscientiousness on positive affect were direct but also indirect, partially mediated by personal projects’ efficacy. Neuroticism had a direct and an indirect effect through a decreased personal projects’ efficacy on the three components of SWB. Extraversion only directly predicted increased positive affect. These findings corroborate the conceptualization that these two types of personality analysis units (Big Five and personal projects) have their own direct, unique and irreducible effect on life satisfaction, positive affect and negative affect. However, their impact on SWB components seems to be also explained through their effect upon personal projects’ efficacy.