The aim of this article is to describe a theoretical framework, i.e., theoretical underpinnings and pedagogical principles, for leadership programs that support managers' evidence-based knowledge of health-promoting psychosocial work conditions, as well as their capability to apply, adapt, and craft sustainable managerial work practices. First, the theoretical framing is introduced, i.e., a system theory that integrates key work conditions with a practical perspective on managerial work and organization. Second, pedagogical principles and measures for leaders' training in integrated handling across system levels are described. Last, we present summarized results from an intervention study applying the theoretical framework and pedagogical principles. The complexity of interactions among different factors in a work system, and the variety in possible implementation approaches, presents challenges for the capability of managers to craft sustainable and health-promoting conditions, as well as the evaluation of the program components. Nevertheless, the evaluation reveals the strength of the program, in providing holistic and context-sensitive approaches for how to train and apply an integrative approach for improving the work environment.