AbstractThis paper presents the main output of the EU‐funded H2020 AGILE 4.0 project: the AGILE 4.0 MBSE‐MDAO Development Framework. The framework aims at connecting upstream Model‐Based Systems Engineering (MBSE) activities to downstream Multidisciplinary Design Analysis and Optimization (MDAO) activities, applied to the development of complex aeronautical systems. Upstream activities include the definition of stakeholders, needs, semantic requirements, and modeling the system architecture design space. Downstream activities include defining, implementing, and executing cross‐organizational and collaborative MDAO workflows to support system synthesis. The development framework is implemented in an Operational Collaborative Environment (OCE), a web‐based platform for project data and modeling tool access. A business jet family design application case demonstrates the use of the development framework and OCE.