The Smart Factory concept describes the extensively networked production of industry 4.0, which affects the entire life cycle of a factory and, in particular, factory planning and factory operation. Both classic and more up-to-date factory planning approaches come to their limits through the new requirements. This paper identifies the requirements that are important for the future structural planning of factories and presents the need for a holistic virtual validation of the factory structure. Furthermore, a methodological approach is addressed for the solution of the challenges.