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Innovation has the potential to improve the quality of care and health service delivery, but maximising the reach and impact of innovation to achieve large-scale health system transformation remains understudied. Interest is growing in three processes of the innovation journey within health systems, namely the spread, sustainability and scale-up (3S) of innovation. Recent reviews examine what we know about these processes. However, there is little research on how to support and operationalise the 3S. This study aims to improve our understanding of the 3S of healthcare innovations. We focus specifically on the definitions of the 3S, the mechanisms that underpin them, and the conditions that either enable or limit their potential. We conducted a scoping review, systematically investigating six bibliographic databases to search, screen and select relevant literature on the 3S of healthcare innovations. We screened 641 papers, then completed a full-text review of 112 identified as relevant based on title and abstract. A total of 24 papers were retained for analysis. Data were extracted and synthesised through descriptive and inductive thematic analysis. From this, we develop a framework of actionable guidance for health system actors aiming to leverage the 3S of innovation across five key areas of focus, as follows: (1) focus on the why, (2) focus on perceived-value and feasibility, (3) focus on what people do, rather than what they should be doing, (4) focus on creating a dialogue between policy and delivery, and (5) focus on inclusivity and capacity building. While there is no standardised approach to foster the 3S of healthcare innovations, a variety of practical frameworks and tools exist to support stakeholders along this journey.