Electrospun micro/nanofibers have gained popularity recently for flexible biomechanical sensors because of their advantages of lightness, compatibility, breathability, mechanical deformability, and function integrability, etc., offering them unprecedented sensitivities and versatilities. With increasing advances in the digital era, existing electrospun flexible sensors are not capable of catering to the demands of multiscenario applications including wearable electronics, interactive interfaces, and real-time continuous health monitoring. To ease and expedite their developments, we thoroughly reviewed their latest progress regarding design, preparation, and optimization. First, a brief overview of the design approaches of electrospun flexible biomechanical sensors based on the working mechanism is highlighted. Then, two kinds of preparation strategies including direct electrospinning and post-treatment-assisted electrospinning are discussed in detail. Further, four means for optimizing the performance and endowing multifunctions to electrospun flexible biomechanical sensors are demonstrated in terms of processing. Accordingly, the challenges and the potential solutions related to this topic are addressed, providing a future direction for the next generation of electrospun flexible biomechanical sensors.