<p>Electronic skin (e-skin) has evolved from rigid silicon-based systems into flexible, multifunctional platforms that emulate the sensory and mechanical properties of human skin. Among various materials, electrospun nanofibers have emerged as a promising substrate for next-generation e-skin due to their notable breathability, mechanical compliance, biocompatibility, and conformability. This review critically examines recent progress in electrospun nanofiber-based e-skins, with a particular emphasis on the synergistic integration of sensing and energy harvesting for autonomous systems. We explore advancements in material selection, structural design, and fabrication techniques, providing insights into electrospinning principles and parameters. The integration of conductive nanomaterials within tailored nanofiber architectures enables multimodal sensing capabilities through piezoresistive, capacitive, and piezoelectric mechanisms. This work highlights key developments across flexible sensors, energy harvesting devices (PENGs, TENGs) and storage solutions, delving into their applications in health monitoring, human–machine interaction (HMI), and environmental sensing. While notable strides have been made, we critically address persistent challenges in large-scale manufacturing, long-term stability, and energy efficiency. The future outlook emphasizes AI-enhanced adaptive systems, neuromorphic signal processing, and sustainable material engineering, providing a strategic framework for developing the next generation of intelligent, self-sufficient e-skin platforms.</p>