Researchers are interested in measuring mental stress because it is linked to a variety of diseases. Real-time stress monitoring via wearable sensor systems can aid in the prevention of stress-related diseases by allowing stressors to be controlled immediately. Physical tests, such as heart rate or skin conductance, have recently been used to assess stress; however, these methods are easily influenced by daily life activities. As a result, for more accurate stress monitoring, validations requiring two or more stress-related biomarkers are demanded. In this review, the combinations of various types of sensors (hereafter referred to as multiplexed sensor systems) that can be applied to monitor stress are discussed, referring to physical and chemical biomarkers. Multiplexed sensor systems are classified as multiplexed physical sensors, multiplexed physical–chemical sensors, and multiplexed chemical sensors, with the effect of measuring multiple biomarkers and the ability to measure stress being the most important. The working principles of multiplexed sensor systems are subdivided, with advantages in measuring multiple biomarkers. Furthermore, stress-related chemical biomarkers are still limited to cortisol; however, we believe that by developing multiplexed sensor systems, it will be possible to explore new stress-related chemical biomarkers by confirming their correlations to cortisol. As a result, the potential for further development of multiplexed sensor systems, such as the development of wearable electronics for mental health management, is highlighted in this review.