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Due to both convergent and divergent characteristics of Industry 4.0 and Lean Production (LP), it is unclear whether their concurrent implementation may increase performance. This paper examines the moderating effect of Industry 4.0 on the relationship between LP and operational performance improvement within a developing economy. A survey was distributed among 147 Brazilian manufacturing companies that had implemented both LP and Industry 4.0. Findings indicate that, although LP’s low setup practices enhance performance, its effect varies when Industry 4.0 practices are also adopted. Managers should thus carefully prioritize the parallel adoption of different bundles of Industry 4.0 and LP practices.