In the era of market globalisation, the quality of products has become a key factor for success in the manufacturing industry. The growing demand for customised products requires a corresponding adjustment of processes, leading to frequent and necessary changes in production control. Quality inspection has been historically used by the manufacturing industry to detect defects before customer delivery of the end product. However, traditional quality methods, such as quality inspection, suffer from large limitations in highly customised small batch production. Frameworks for quality inspection have been proposed in the current literature. Nevertheless, full exploitation of the Industry 4.0 context for quality inspection purpose remains an open field. Vice-versa, for quality inspection to be suitable for Industry 4.0, it needs to become fast, accurate, reliable, flexible, and holistic. This paper addresses these challenges by developing a multi-layer quality inspection framework built on previous research on quality inspection in the realm of Industry 4.0. In the proposed framework, the quality inspection system consists of (a) the work-piece to be inspected, (b) the measurement instrument, (c) the actuator that manipulates the measurement instrument and possibly the work-piece, (d) an intelligent control system, and (e) a cloud-connected database to the previous resources; that interact with each other in five different layers, i.e., resources, actions, and data in both the cyber and physical world. The framework is built on the assumption that data (used and collected) need to be validated, holistic and on-line, i.e., when needed, for the system to effectively decide upon conformity to surpass the presented challenges. Future research will focus on implementing and validating the proposed framework in an industrial case study.