Lean Six Sigma is a powerful methodology that integrates the best of two distinct approaches to business excellence: Lean and Six Sigma. While Six Sigma focuses on the systematic reduction of variation within processes, the Lean approach aims for business growth through waste elimination and the continuous development of people. Given the advent of Industry 4.0, digitalization now presents the next frontier of industrial improvement. Lean Six Sigma can be integrated with Industry 4.0 to optimize process efficiency. This study is a systematic literature review on the integration of Industry 4.0 and Lean Six Sigma. The findings are that while this topic is an emerging area of study, there are benefits, motivations, critical success factors, and challenges to integrating Lean Six Sigma and Industry 4.0.