Abstract: Network of vehicle to everything (V2X) can realize the connections among human beings, vehicles, road side units (RSU) and even the cloud, assisted by novel information and communication techniques. In future, B5G/6G will enable the next-generation V2X to perform superior communications and sensing so as to facilitate more advanced applications, such as intelligent driving and transportation. However, the strong doppler effects caused by high mobility of vehicles will extremely increase inter carrier interference and pilot overhead of the existing Orthogonal Frequency Division Multiplexing (OFDM) system, especially in the future B5G/6G eras when mmWave and Terahertz are widespread. In recent years, Orthogonal Time Frequency Space (OTFS) techniques are getting wide attentions due to the advantages in resisting doubly-selective fading. The integrated sensing and communication (ISAC) in V2X based on OTFS has become one hot topic. Our main purpose is to analyze and summarize the key techniques, applications and challenges of OTFS-ISAC in V2X. First, we introduce the structure of OTFS system compatible with OFDM, and illustrate its performance in both communication and sensing. Secondly, we discuss the key techniques of OTFS-ISAC from the aspects of frame structure in physical layer, pilot mechanisms and ISAC receivers. Finally, we investigate case studies of OTFS-ISAC in V2X and then analyze the corresponding main challenges.