In the past few years, the implementation of a more sustainable mode of production has become necessary for manufacturing companies to thrive in the international business context. Professionals and researchers are also paying increasing attention to Industry 4.0 (I4.0) and big data, as well as Circular Economy (CE) concepts, due to the many advantages they can provide for the manufacturing industry. The purpose of the CE is the effective utilization of resources, and the I4.0 concept has been established to help achieve this objective and requires further exploration in the field of sustainable production. Research gaps exist in the literature regarding challenges to I4.0 and CE in terms of Sustainable Footwear Production (SFP) in emerging economies. Therefore, the purpose of this study is to deliver an original analysis of the most significant challenges regarding the interaction of I4.0 and CE for SFP. A comprehensive literature review is performed to establish the challenges to I4.0-CE for SFP in the context of emerging economies. Further, the challenges identified are prioritized based on the assessment of a real case study from the footwear industry. A mixed methodology (i.e., both qualitative and quantitative) is adopted to identify the cause-effect interactions among the identified challenges. The results of our analysis show that the five most important causal challenges obstructing the execution of SFP in the footwear industry are ‘deficient legislative-industry strategies towards SFP adoption’, ‘lack of competence in I4.0 and CE concepts for SFP adoption’, ‘understanding of synchronization among suppliers for attaining SFP’, ‘uncertain economic benefits of I4.0 and CE application for attaining SFP’ and ‘inadequate support for industries towards SFP efforts’. This study may be beneficial for industry managers, practitioners and decision makers to establish an understanding of I4.0-CE initiatives and to mitigate the most significant challenges regarding the successful implementation of I4.0-CE for SFP.