<p>The rapid evolution of industrial systems demands a careful reconciliation of sustainability goals, beyond organizational success and financial profitability. While Industry 4.0 (I4.0) has driven significant advances in automation and process efficiency, its impact on the Sustainable Development Goals (SDGs) remains limited and primarily focused on economic outcomes. Responding to the need for deeper integration between digital transformation and sustainability, this study aims to map the existing literature on Lean Six Sigma (LSS) in the contexts of I4.0 and Industry 5.0 (I5.0), but also, to clarify how sustainability dimensions can be embedded into LSS practices. To achieve this, a scoping review was conducted, including all scientific research published up to submission date and sourced from reliable databases (Scopus and others). Through this comprehensive review, a notable gap in how LSS addresses the various dimensions of SDGs was identified. To address this, the present work introduces a novel conceptual framework —Lean Six Sigma 5.0 (LSS 5.0)— which repositions traditional process improvement tools within a human-centric, resilient, and sustainability-oriented manufacturing paradigm. This innovative model advances Sustainable Manufacturing (SM) by embedding sustainability at the core of quality and continuous improvement strategies, enabling organizations to respond to the evolving expectations of I5.0. Beyond its theoretical contribution, this work offers practical insights for industries seeking to align LSS initiatives with the broader goals of sustainable development. Given its theoretical nature, future research should validate this model through empirical case studies and industrial applications, supporting innovation in SM. The findings directly address the review’s objectives by mapping existing knowledge and proposing actionable pathways for integrating sustainability within LSS practices in the I5.0 era.</p>