Xinwei Zhang, Hanying Wang, Shusen Zheng, Zhuoran Hu, Yuhan Gao, Tuotuo Zhang, Nanke Chen, Zhipeng Zhang, Yao Sun, Junrong Li
Surface‐enhanced Raman spectroscopy (SERS) has emerged as a powerful analytical tool in biomedical diagnostics and environmental monitoring, owing to its multiplex detection capability, ultrahigh sensitivity, and excellent resistance to fluorescence interference. The performance of SERS is critically dependent on the rational design of active substrates, which significantly enhance signal intensity and reproducibility. This review discusses the fundamental mechanisms underlying SERS enhancement, including both electromagnetic and chemical contributions, and systematically summarizes key design principles for high‐performance SERS substrates. Special emphasis is placed on the engineering of noble metals (e.g., Au, Ag), semiconductors (e.g., TiO 2 , ZnO), metal–organic framework composites, and hydrogel‐based substrates, highlighting their respective advantages and optimization strategies. Furthermore, we explore applications of SERS in early cancer diagnosis and rapid pathogen detection, and discuss the challenges and future directions for the further development of SERS technology.