A novel high-voltage powerline inspection system was investigated, which consists of the cooperated ground vehicle and drone. The ground vehicle acts as a mobile platform that can launch and recycle the drone, while the drone can fly over the powerline for inspection within limited endurance. This inspection system enables the drone to inspect powerline networks in a very large area. Both vehicle’ route in the road network and drone’s routes along the powerline network have to be optimized for improving the inspection efficiency, which generates a new Two-Layer Point-Arc Routing Problem (2L-PA-RP). Two constructive heuristics were designed based on “Cluster First, Route Second” and “Route First, Split Second”. Then, local search strategies were developed to further improve the quality of the solution. To test the performance of the proposed algorithms, different-scale practical cases were designed based on the road network and powerline network of Ji’an, China. Sensitivity analysis on the parameters related to the drone’s inspection speed and battery capacity was conducted. Computational results indicate that technical improvement on the inspection sensor is more important for the cooperated ground vehicle and drone system.