“Industry 4.0” is recognized as the future of industrial production in which concepts as Smart Factory and Decentralized Decision Making are fundamental. This paper proposes a novel strategy to support decentralized decision, whilst identifying opportunities and challenges of Industry 4.0 contextualizing the potential that represents industrial digitalization and how technological advances can contribute for a new perspective on manufacturing production. It is analysed a set of barriers to the full implementation of Industry 4.0 vision, identifying areas in which decision support is vital. Then, for each of the identified areas, the authors propose a strategy, characterizing it together with the level of complexity that is involved in the different processes. The strategies proposed are derived from the needs of two of Industry 4.0 main characteristics: horizontal integration and vertical integration. For each case, decision approaches are proposed concerning the type of decision required (strategic, tactical, operational and real-time). Validation results are provided together with a discussion on the main challenges that might be an obstacle for a successful decision strategy.