Abstract : Research work presented in this manuscript deals with interoperability issues in the domain of Product Lifecycle Management (PLM) and aims at proposing a methodology able to remedy it. We define the objective of PLM as the control of the complexity that characterizes the development and monitoring of the product. In this context, the objective of the interoperability is to control the interactions between components of this PLM complex system. We demonstrate that this objective is reached if we ensure the continuity and the conservation of the semantic flow inside the system. Our study is restricted to design and production fields, but can be extended to other domains. The continuity of the semantic flow is guaranteed by an architecture that we entitled “service-oriented multi-layered mediation”. The main part of this architecture, the mediator, takes care to orientate the semantic flows towards the adequate systems, and semantically connect the exchanged information by relying on an unification meta-model. We demonstrate that, to ensure the robustness the flexibility and the agility of the so-constituted system, the choice of a generic and extensible standard meta-model should be favored. We thus proposed a mapping of STEP standard allowing to choose the adequate meta-model. We illustrate the choice and the definition of this meta-model in the case of two interoperability problems in the design and production domains: the interoperability CAD/PDM and the interoperability PDM/ERP. We illustrate our methodology in the implementation of the PLCS standard. Moreover, we introduce a model of product semantic tags that allows to rebuild the multiple product views corresponding to different actor needs. A set of demonstrators validate our propositions and our results.