The competitive market pressures organizations to maximize profits, reduce resource consumption, and eliminate waste, necessitating the manufacturing industry to enhance its competitiveness and bolster its role in the local and national economy. Despite its importance, the integration of Lean Six Sigma (LSS) and Industry 4.0 (I4.0) within the manufacturing industry needs to be studied more. This study investigates existing frameworks, applications, and challenges of incorporating LSS and I4.0 in manufacturing through a systematic literature review (SLR) and bibliometric analysis of 30 publications from the Scopus database since the emergence of this integration. The findings reveal the need for a strategic, comprehensive, and practical framework to guide the manufacturing sector in adopting LSS and I4.0. Applying LSS along with I4.0 leads evidently to greater efficiency, lower operational costs, improved productivity, enhanced customer satisfaction, and better quality. This research provides practitioners, academics, and professionals with valuable insights into integrating LSS and I4.0 in manufacturing and its impact on organizational performance. However, the quality of available literature and potential biases in the selected search terms and databases represent significant limitations of the study.The competitive market pressures organizations to maximize profits, reduce resource consumption, and eliminate waste, necessitating the manufacturing industry to enhance its competitiveness and bolster its role in the local and national economy. Despite its importance, the integration of Lean Six Sigma (LSS) and Industry 4.0 (I4.0) within the manufacturing industry needs to be studied more. This study investigates existing frameworks, applications, and challenges of incorporating LSS and I4.0 in manufacturing through a systematic literature review (SLR) and bibliometric analysis of 30 publications from the Scopus database since the emergence of this integration. The findings reveal the need for a strategic, comprehensive, and practical framework to guide the manufacturing sector in adopting LSS and I4.0. Applying LSS along with I4.0 leads evidently to greater efficiency, lower operational costs, improved productivity, enhanced customer satisfaction, and better quality. This research provides practitioners, academics, and professionals with valuable insights into integrating LSS and I4.0 in manufacturing and its impact on organizational performance. However, the quality of available literature and potential biases in the selected search terms and databases represent significant limitations of the study.