Flexible strain sensors have gained significant attention as wearable electronic devices because of their adaptability and versatility. Developing high-performance flexible strain sensors with hydrophobic and photothermal properties is a promising avenue for fabricating smart wearable electronic devices. In this study, MXene and carbon nanotubes (CNTs) were coated on a thermoplastic polyurethane (TPU) nanofiber membrane using ultrasonic dipping and spraying strategies. Flexible strain sensors with hydrophobic properties were obtained by encapsulation of the membrane with polydimethylsiloxane (PDMS). The PDMS-MXene@CNT/TPU nanofiber membrane-based flexible strain sensor demonstrated exceptional performance, exhibiting exceedingly low detection limits (0.05%), a rapid response time (70 ms), high sensitivity (GF = 11 393), and exceptional stability (2000 cycles under 30% strain) and durability under stretch-release testing. Additionally, the sensor maintained hydrophobic performance, as evidenced by a water contact angle of 117°. The outstanding sensing performance of the sensor makes it highly adaptable for various smart wearable electronic applications in monitoring human motion and health status; in addition, its photothermal and hydrophobic properties enhance its suitability for deployment in humid and cold environments.