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Introduction: Organizations are increasingly concerned with attracting and retaining talent, making it essential to understand the factors beyond the promotion of well-being and organizational success. The present study had the main goal of analyzing the relationships between human personal values, the meaning of work, organizational commitment and climate, job satisfaction, and work well-being. Materials and Methods: A convenience sample of 470 working Portuguese participants was collected, with 68.3% females, aged from 18 to 65 years old, and studied through an online research protocol. Results: The studied variables correlated in the expected direction. Empirical tests of the proposed conceptual model showed that personal values and organizational commitment had a direct effect on job satisfaction and organizational commitment had a direct effect on work well-being. These effects were differentially explained by organizational climate and the meaning of work. When considering the dimensions of organizational climate as mediators, the direct effects were maintained but different dimensions emerged as specific mediators: support mediated the relationship between personal values and organizational commitment with job satisfaction; a rules-oriented climate mediated the relationship between organizational commitment with work well-being. In both models, the meaning of work mediated the relationship between organizational commitment with work well-being but not the relationship between personal values and organizational commitment with job satisfaction. Conclusions: The obtained results were discussed based on the literature and their implications for organizational contexts, highlighting the relevance of different factors for the promotion of job satisfaction and well-being and, in consequence, healthy workplaces.