An area of promising research is formed by the core self-evaluation construct. The aim of this study is to investigate the relationship between this construct and job satisfaction, evaluating the role played by gender. The following instruments were administered to 385 subjects of the Florentine care system (A.S.L.10): Rosenberg Self-Esteem Scale, Occupational Self-Efficacy Scale, Work Locus of Control Scale, Eysenck Personality Questionnaire, Organization Satisfaction Questionnaire. Descriptive statistics, correlations, ANOVA and hierarchical regressions were conducted. The core selfevaluation traits, and particularly, the work locus of control emerge as highly significant predictors of job satisfaction. The results provide a more in-depth look at the relationship between core self-evaluation and job satisfaction, delineating new research hypotheses and highlighting the importance of adequate intervention.