This realist review aims, with evidence from recent studies, to understand both how nurse-led case management interventions are implemented in the management of chronic illnesses, and in what circumstances these interventions are successful. The review followed the realist review methodology. From four electronic databases, twenty empirical and primary nurse-led case management intervention studies published between January 2011 and February 2020 were included. For each study, causality was explored, and findings were integrated. Three contexts, five mechanisms, and three major outcomes were found, and several context–mechanism–outcome strings were identified. Further analysis and synthesis of the studies showed that when duration of intervention, service delivery mode, and types of services are appropriate, as well as number of services with patients considering care is provided, case managment interventions change outcomes for patients with chronic illnesses. Finally, an explanatory conceptual framework based on the review results was developed to guide nurse managers and researchers.