The automation and intelligence highlighted in Industry 4.0 put forward higher requirements for reasonable trade-offs between humans and machines for decision-making governance. However, in the context of Industry 4.0, the vision of decision support for design engineering is still unclear. Additionally, the corresponding methods and system architectures are lacking to support the realization of value-chain-centric complex engineered systems design lifecycles. Hence, we identify decision support demands for complex engineered systems designs in the Industry 4.0 era, representing the integrated design problems at various stages of the product value chain. As a response, in this paper, the architecture of a Knowledge-Based Design Guidance System (KBDGS) for cloud-based decision support (CBDS) is presented that highlights the integrated management of complexity, uncertainty, and knowledge in designing decision workflows, as well as systematic design guidance to find satisfying solutions with the iterative process “formulation-refinement-exploration-improvement” (FREI). The KBDGS facilitates diverse multi-stakeholder collaborative decisions in end-to-end cloud services. Finally, two design case studies are conducted to illustrate the proposed work and the efficacy of the developed KBDGS. The contribution of this paper is to provide design guidance to facilitate knowledge discovery, capturing, and reuse in the context of decision-centric digital design, thus improving the efficiency and effectiveness of decision-making, as well as the evolution of decision support in the field of design engineering for the age of Industry 4.0 innovation paradigm.