Recently, the Ti3C2Tx MXene-based flexible electronics have sparked wide attention in artificial health diagnosis, military security and human–machine interaction. High sensitivity, durability and multifunctionality are desired for strain sensors in long-term health detection. However, unevenness and low fastness of MXene and stretchable nanofibers lead to poor sensitivity and durability, building a strong interface to combine the two-dimensional (2D) MXene nanosheets uniformly along the 1D nanofibers and form a 3D connected electrical network benefits to the improvement of sensing performances. Herein, we propose a facile strategy to prepare a breathable and multifunctional all-nanofiber sensor based on MXene and styrene–butadiene–styrene (SBS) nanofibers. Firstly, the molecular chain of SBS introduces quaternary ammonium groups (NSBS) by thiol-ene click chemistry, hydrophilicity and mechanical properties of NSBS nanofibers are significantly improved, then MXene nanosheets can uniformly and firmly adsorb along with NSBS nanofibers by electrostatic interaction. The assembled MXene/NSBS sensor reaches an ultrahigh sensitivity of 62,194 in the wide detection range of 300% and stability over 3000 cycles for human joint motion, pulse and ECG signal wireless detection. Furthermore, the MXene/NSBS electrodes demonstrate temperature response and thermal management performance including Joule heating and photothermal performance. Consequently, this work indicates a promising candidate for real-time health diagnosis and artificial intelligence in next-generation multifunctional devices.