<p>Flexible pressure sensors, which detect pressure changes on a flexible substrate, are extensively employed across a diverse range of emerging applications, including intelligent control and wearable sensing. They have attracted considerable research attention owing to their remarkable flexibility, sensitivity, and lightweight properties. Currently, the development of multifunctional devices presents significant challenges for the design of flexible pressure sensors. In addition to exploring new functional materials and sensing mechanisms, the establishment of surface microstructures has become the key element in the design of desired pressure sensors. These microstructures improve critical sensor performance metrics such as sensitivity and detection range by increasing contact area, inducing localized stress concentration, or modulating interfacial mechanical properties. Herein, the review summarizes the characteristics, fabrication methods, sensing enhancement strategies, and applications of the typical surface microstructures in flexible pressure sensors. The development trends, design principles, comparative advantages, and limitations of the surface microstructures are the focus of discussion. This study offers a forward-looking perspective on the design strategy of surface microstructures in diverse pressure-sensing scenarios, thereby facilitating their broader implementation in medical monitoring, human–machine interaction, and smart electronic systems.</p>