Manufacturing, generating wealth and jobs by fully exploiting knowledge and resources, is the fundamental enabler and sustainer of Europe’s Competitive and Sustainable Development. Manufacturing in Europe provides presently 41,5 % of the added-value (over €1,535 million) and 30,4 % of the employment (34 million people), with each job at the factory floor generating two other jobs in services. Manufacturing in Europe is presently under threat and in crucial and urgent need to add value and decrease costs by embedding design and technology, as to compensate for the fierce competition from the emerging economies. The need to keep manufacturing operations and jobs in Europe calls for industry transformation, as to ensure strong cost reductions, increased flexibility and smaller response times while keeping high standards in product quality with increasing complex novel products. But the ability to manage increased product complexity, by spreading subcontracting and outsourcing, cannot be achieved without building collaborative networks over the complete supply and value chain. Enterprise interoperability is thus a stringent requirement in highly competitive manufacturing value chains. And it is also an emergent one if we want to be able to design and deploy a competitively sustainable European Production System, through the use of disruptive technological processes enabled by digital production.