Vehicle-to-everything (V2X) communication in the vehicular ad hoc network (VANET), an infrastructure-free mechanism, has emerged as a crucial component in the advanced Intelligent Transport System (ITS) for special information transmission and inter-vehicular communications. One of the main research challenges in VANET is the design and implementation of network routing protocols which manage to trigger V2X communication with the reliable end-to-end connectivity and efficient packet transmission. The organically changing nature of road transport vehicles poses a significant threat to VANET with respect to the accuracy and reliability of packet delivery. Therefore, a position-based routing protocol tends to be the predominant method in VANET as they overcome rapid changes in vehicle movements effectively. However, existing routing protocols have some limitations such as (i) inaccurate in high dynamic network topology, (ii) defective link-state estimation (iii) poor movement prediction in heterogeneous road layouts. In this paper, a target-driven and mobility prediction (TDMP) based routing protocol is therefore developed for high-speed mobility and dynamic topology of vehicles, fluctuant traffic flow and diverse road layouts in VANET. The primary idea in TDMP is that the destination target of a driver is included in the mobility prediction to assist the implementation of the routing protocol. Compared to existing geographic routing protocols which mainly greedily forward the packet to the next-hop based on its current position and partial road layout, TDMP is developed to enhance the packet transmission with the consideration of the estimation of inter-vehicles link status, and the prediction of vehicle positions dynamically in fluctuant mobility and global road layout.