Although many routing algorithms have been developed, it is difficult for designers in the automotive industry to adopt them because of the complicated preliminary steps that are required. This study presents a systematic framework for generating the routing layout of the tubes, hoses, and cable harnesses in a commercial truck. The routing layout design problem in a commercial truck is analysed and defined. For routing operations, a sequential graph-based routing algorithm is employed to rapidly provide a routing solution. Because a reference routing layout design does not exist in most engineering problems, a cell-based genetic algorithm combined with a modified maze algorithm is employed to generate a reference design. To consider the clamping condition of the routing components, a new fitness function in the genetic algorithm is implemented. The numerical study shows that the proposed routing algorithm provides a better reference routing layout design than the conventional algorithm. The proposed automatic design system was applied to the routing layout design problem of a commercial truck. It was demonstrated that the proposed framework satisfies all industrial practitioners’ functional requirements and provides a systematic method of solving the routing layout design problem, considering all its characteristics.