Industry 4.0 initiatives can influence whole business system via transforming the means the products are designed, produced, delivered and discarded. Industry 4.0 is relatively novel to developing nations, especially in India and needs a clear definition for proper understanding and practice in business. This paper aims to recognize key challenges to Industry 4.0 initiatives and analyze the identified key challenges to prioritize them for effective Industry 4.0 concepts for supply chain sustainability in emerging economies by taking Indian manufacturing industry perspective. Industry 4.0 initiatives can help industries to incorporate environmental protection and control initiatives as well as process safety measures in supply chains towards sustainable supply chains. However, adoption of Industry 4.0 initiatives is not so easy due to existence of many challenges. Therefore, the present research identifies 18 key challenges to Industry 4.0 initiatives for developing supply chain sustainability using an extensive literature review. These challenges were analyzed through 96 responses received from Indian manufacturing sector using a questionnaire based survey. Explanatory Factor Analysis results classified identified challenges into four key dimensions of challenges. Analytical Hierarchy Process further ranks the identified dimensions of challenges and related challenges. Findings of the study revealed that Organizational challenges holds the highest importance followed by Technological challenges, Strategic challenges, and Legal and ethical issues. This work is very useful for practitioners, policy makers, regulatory bodies and managers to develop an in-depth understanding of Industry 4.0 initiatives and eradicate the potential challenges in adopting Industry 4.0 initiatives for supply chain sustainability. (C) 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.