The design process of flow-oriented assembly systems is characterized by being both highly complex and time consuming. Especially those design processes categorized into robotic and multi variant encountered in the automotive body-in-white production stages. Unlike established manual and template-based assembly system design models, which are currently applied in industry, the here presented novel approach uses a knowledge-based search algorithm and automatically generates optimal assembly system configurations. The algorithm has been implemented in a software prototype and the results have been validated against different largesize industrial scenarios in the automotive field of body-in-white production.