PurposeMicro, Small, Medium Enterprises (MSMEs) are witnessing an accelerated transformation by the advent of Industry-4.0 (I4.0) in the post-pandemic period. It is offering promising customer responsiveness, competitiveness, business growth and sustainability and thereby, compelling its integration to MSMEs. Therefore, it is imperative for researchers to explore Industry 4.0 challenges and their specific implementation requirements and also provide useful insights to the stakeholders.Design/methodology/approachThis research paper has identified, explained and analysed various determinants of the I4.0 implementation, in MSME context. Focus group approach has been applied for taking inputs from experts for developing the House of Quality (HOQ) tool of the Quality Function Deployment (QFD) methodology from the Total Quality Management (TQM) tool-box.FindingsBased on the responses and after applying QFD, a conceptual model suggesting relevant strategies to execute I4.0 by Indian MSMEs has been developed. The model highlights three key challenges being faced by the Indian MSMEs –Top management support, Incompatible resources and Transition cost. The model also reveals vital few designer's descriptors – Cultural reorientation, IT enabled digitization, Process automation and knowledge and skill in I4.0 implementation (Knowhow) for a structured implementation of I4.0.Practical implicationsThe evolved HOQ framework has provided some useful insights - priority areas in the MSME challenges and the designer's descriptors for I4.0 implementation in MSME. The research has also provided the understanding of the dynamics between the I4.0 components through the 10 × 10 interrelationship matrix of the HOQ. Farsighted MSME leaders, practising consultants, sourcing managers and policy makers can use the developed framework as a reference in formulating tactics to mitigate the I4.0 implementation barriers.Originality/valueThe non-conventional application of HOQ in the QFD approach from the TQM tool-box is a useful value addition to the TQM practitioners. The useful insights to the MSME leaders, policy makers, sourcing managers of OEM, consultants engaged in I4.0 transformation and academic researchers are the other contribution.