PurposeIn the evolving landscape of Industry 5.0 (I5.0), which emphasises sustainability, human-centricity and resilience, mapping the current interrelationship and future research directions, the role of Lean Six Sigma (LSS) methodology remains underexplored. Our study addresses this gap by examining the potential of LSS to support I5.0 while identifying areas for further investigation.Design/methodology/approachThis study's multifaceted approach, which includes systematic literature review (SLR), bibliographic network analysis (BNA) and expert validation (EV), provides a holistic exploration of the interaction between LSS and I5.0 as the basis for well-founded conclusions.FindingsThe analysis yields several valuable insights. Firstly, it demonstrates the absence of a direct link between LSS and I5.0. Secondly, the substantial body of literature analysed establishes connections between LSS and its pillars. Thirdly, the analysis identifies points of intersection, difference and similarity between LSS and I5.0, highlighting the potential of LSS to facilitate implementation of I5.0 through its proven methodologies, continuous improvement culture, risk management, error learning, human–machine collaboration and training and skill development.Originality/valueThis study pioneers the effort to realise the latent potential of LSS in the context of I5.0. Its systematic identification of the synergies between these paradigms fills a critical gap in the literature and gives policymakers, managers and researchers a guide for informed decision-making to maximise the benefits of I5.0 for individuals, companies, society and the planet.