High-performance flexible strain sensors with synergistic and outstanding thermal regulation function are poised to make a significant impact on next-generation multifunctional sensors. However, it has long been intractable to optimize the sensing performance and high thermal conductivity simultaneously. Herein, a novel flexible sandwich-like strain sensor with advanced thermal regulation capability was prepared by assembling electrospun thermoplastic polyurethane (TPU) fibrous membrane, MXene layer, and TPU/boron nitride nanosheet (BNNS) composite films. The as-prepared sensor demonstrates a wide strain working range (∼100% strain), an ultrahigh gauge factor (2080.9), and a satisfactory reliability. Meanwhile, benefiting from the uniform dispersion and promising orientation of BNNSs in TPU composites, the sensor possesses a high thermal conductivity of 1.5 W•m −1 •K −1 , guaranteeing wearer comfort. Additionally, the unique structure endows the sensor with high stretchability, breathability, biocompatibility, and tunable electromagnetic interference shielding performances. Furthermore, an integrated wireless motion monitoring device based on this sensor is rationally designed. It exhibits a fast response time, a wide recognition range, and the ability to maintain skin temperature during prolonged physical activity. These encouraging findings provide a new and feasible approach to designing high-performance and versatile flexible strain sensors with broad applications in advanced wearable technology.