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The emerging industrial revolution referred to as Industry 5.0 is focusing on leveraging human creativity with intelligent and autonomous systems to derive user-friendly work environment for the businesses. Industry 5.0 stresses on people centric work ecosystem, zero accident policy and the well-being of labour within the production processes. This approach of Industry 5.0 to obtain human-centric safety solutions through the deployment of digital technologies deduces workplace accidents and costs leading to the development of Safety 4.0. This chapter aims to investigate the opportunities and challenges of Safety 4.0 and its enabling technologies aspiring towards the greater impact on safety management. Further, we have proposed a framework for the role of human centric digital transformations concerning safety in the manufacturing industry propelling Safety 4.0. Concluding, we discuss the implications for managers and practitioners. We found that Safety 4.0 will strengthen industrial safety, and instead of reacting to accidents, the concept evolved towards a preventive and proactive approach for a healthy industrial ecosystem.