Manufacturing companies operating in global production networks face rising complexities and increasing susceptibilities to disruptions. For coping with disruptions, companies are in need of a holistic, comprehensive disruption management, involving all network actors to find optimal measures. However, today’s disruption management approaches are characterized by intuitive, experienced-based reactions, limiting themselves to solely the production or the logistics perspective and hence not permitting an overarching reaction. Therefore, this paper presents an integrated approach to disruption management, combining the production and logistics perspectives. It incorporates DoE and metamodelling methods in a simulation model to enable efficient, robust decision-making in highly complex environments.