With the increase in the size and weight of 300-mm wafers, manual handling has become difficult and automated material handling systems (AMHS) are necessary. The 300-mm fab requires only one type of vehicle and rail to connect all of the process resources, allowing vehicles to travel directly between intrabay and interbay systems. This type of transportation is a direct tool-to-tool transportation strategy. This paper aims to analyse the impact of direct tool-to-tool transportation. The present study used a discrete-event simulation to create a 300-mm semiconductor manufacturing flow and executed a factorial experiment of three factors based on uniform design, including the direct ratio, the stocker capacity and the number of machine load ports. Finally, using the dual-response surface method, the most important of the three factors and the best performance were determined. The results show promise for the proposed tool-to-tool transportation strategy in solving a practical application.