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PurposeThe study proposes to determine the impending challenges to lean integration with Industry 4.0 (I4.0) in manufacturing that aims at achieving desired operational performance. Integrating lean and Industry 4.0 as the two industrial approaches is synergetic in providing operational benefits such as increasing flexibility, improving productivity, reducing cost, reducing delivery time, improving quality and value stream mapping (VSM). There is an urgent need to understand the integrated potential of OPEX strategies like lean manufacturing and also to determine the challenges for manufacturing SMEs and further suggest a strategic roadmap for the future.Design/methodology/approachThe current work has used a combined approach on interpretative structural modeling (ISM) and fuzzy Matrice d'impacts croisés multiplication appliquée á un classment (MICMAC) approach to structure the multiple level analysis for the implementation challenges to integrate OPEX strategies with Industry 4.0.FindingsThe research has found that the indulgence of various implementation issues like lack of standardization, lack of vision and lack of trained support, all are the major challenges that inhibit the integration of OPEX strategies with I4.0 technologies in manufacturing.Research limitations/implicationsThe research has investigated the internal factors acting as a roadblock to lean and Industry 4.0 adoption. Further studies may consider external factors to lean and Industry 4.0 implementation. Also, further research may consider other operational excellence approaches and extend further to relevant sectors.Practical implicationsThis study provides the analysis of barriers that is useful for the managers to take strategic actions for implementing OPEX strategies with I4.0 in smart manufacturing.Originality/valueThe research determines the adoption challenges towards the integrated framework. This is the first study to explore challenges in integrating OPEX strategies with I4.0 technologies in manufacturing SMEs.