A wide variety of biotic and abiotic stresses continually attack plants and animals, which adversely affect their growth, development, reproduction, and yield realization. To survive under stress conditions, highly sophisticated and efficient tolerance mechanisms have been evolved to adapt to stresses, which consist of the variation of effector molecules playing vital roles in physiological regulation. The development of a sensitive, facile, and rapid analytical methods for stress factors and effector molecules detection is significant for gaining deeper insight into the tolerance mechanisms. As a nondestructive analysis technique, surface-enhanced Raman spectroscopy (SERS) has unique advantages regarding its biosensing applications. It not only provides specific fingerprint spectra of the target molecules, conformation, and structure, but also has universal capacity for simultaneous detection and imaging of targets owing to the narrow width of the Raman vibrational bands. Herein, recent progress on biotic and abiotic stresses, tolerance mechanisms and effector molecules is summarized. Moreover, the development and promising future trends of SERS detection for stress-related substances combined with nanomaterials as substrates and SERS tags are discussed. This comprehensive and critical review might shed light on a new perspective for SERS applications.