The use of a dyad leadership model involving a physician co-leader and a co-leader with a different background, the dyad co-leader, is gradually increasing in Healthcare Organizations (HCOs). There is a paucity of empirical studies on various aspects of this model. This study’s aim was to identify challenges and strategies for success in the dyad leadership model in healthcare. Through a mixed-methods approach utilizing focus groups, surveys, and semi-structured interviews, perceptions of 37 leaders in one HCO at different hierarchical levels were analysed based on their lived experiences. The challenges and success strategies spanned personal, interpersonal, and organizational domains. The areas requiring attention included mindsets, competencies, interpersonal relationship, support, time, communication, and collaboration. In addition, the importance of organizational context addressing its structure, strategy, operations, and culture was highlighted. The findings from this study may be used for praxis, development, and implementation of dyad leadership.