Lean is and will still be one of the most popular management philosophies in the Industry 4.0 context and simulation is one of its key technologies. Many authors discuss about the benefits of combining Lean and simulation to better support decision makers in system design and improvement. However, there is a lack of reviews in the domain. Therefore, this paper presents a four-stage comprehensive review and analysis of existing literature on their combination. The aim is to identify the state of the art, existing methods and frameworks for combining Lean and simulation, while also identifying key research perspectives and challenges. The main trends identified are the increased interest in the combination of Lean and simulation in the Industry 4.0 context and in their combination with optimisation, Six Sigma, as well as sustainability. The number of articles in these areas is likely to continue to grow. On the other hand, we highlight six gaps found in the literature regarding the combination of Lean and simulation, which may induce new research opportunities. Existing technical, organisational, as well as people and culture related challenges on the combination of Lean and simulation are also discussed.