Evidence points to an indirect relationship between transformational leadership (TFL) and employee well-being, and numerous work characteristics have been identified as mediators. However, the relative mediating effect of different types of job resources and job demands on the TFL–well-being relationship remains unclear, rendering it impossible to determine which ones are the most influential. This study aims to provide a comprehensive analysis of the relative mediation potential of different work characteristics in the TFL–well-being relationship in multiple three-level meta-analytical structural equation models of 243 samples. Based on the JD–R Model, this study extends this theoretical framework by suggesting TFL as a predisposing variable that influences both job resources and job demands, leading to changes in indicators of both positive and negative employee well-being. The results show that, while all the examined job resources and demands mediated the TFL–well-being relationship, organizational resources were identified as the strongest mediators. Furthermore, job demands had a strong mediating effect on the relationship between TFL and negative well-being, while job resources more strongly mediated TFL and positive well-being. We present a differentiated picture of how transformational leaders can influence their employees’ well-being at the workplace, providing valuable knowledge for future research and practice.