Mastering Material Handling Systems is a crucial issue for numerous companies since the costs of Material Handling activities are far from being negligible. The demand for a sustainable industry and the introduction of industry 4.0 technologies for Material Handling are renewing the Material Handling System design concerns. Many questions arise on whether it is suitable or not to bring technologies such as Autonomous Mobile Robots or Real-Time Location Systems to the shop-floors. In the presented study, various companies are questioned on their utilization of new technologies and on their processes to manage and modify their Material Handling System. It appears that practices in Material Handling System design and management are diversified and that no consensus exists on how to efficiently design these systems. A cross-analysis is performed to identify the differences and the common patterns between the literature and the field study. This work discusses the need to better understand the relation between the different aspects of Material Handling System design and presents key challenges to be addressed in the context of industry 4.0. To address these challenges, research directions are proposed. They are composed of four main challenges area: Material handling specifications, Material Handling Equipment selection, Material Handling Equipment deployment, and Material Handling System analysis.