In response to emergent challenges, lean philosophy became one of the most common approaches implemented in healthcare operations. Although lean has been widely implemented, there is still a lack of understanding of the factors that impact value creation in healthcare. Thus, this study aims to identify the factors that impact the implementation and sustainability of lean and value creation in the healthcare ecosystem. We conducted a systematic literature review of 156 articles, and our findings are two-fold: first, we present descriptive results as an outline of the extant literature on lean in healthcare, such as areas of applications, methods, tools, and success and failure cases in different areas of healthcare. Second, we present prescriptive findings and analyse overarching themes (n = 9) representing significant barriers and enablers of the lean journey. Our study provides implications to the knowledge by offering a multi-level framework that touches staff and stakeholders (people-level), operations and technology (process-level), and organisations and leadership (resources-level). This framework illustrates the impact on value creation/destruction and the need for balanced centricity in the healthcare ecosystem. Finally, we establish a future research agenda with six overarching themes and 18 research questions for scholars and managers to explore the lean journey further.