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Abstract Recent developments of micro‐sensors and flexible electronics allow for the manufacturing of health monitoring devices, including electrocardiogram (ECG) detection systems for inpatient monitoring and ambulatory health diagnosis, by mounting the device on the chest. Although some commercial devices in reported articles show examples of a portable recording of ECG, they lose valuable data due to significant motion artifacts. Here, a new class of strain‐isolating materials, hybrid interfacial physics, and soft material packaging for a strain‐isolated, wearable soft bioelectronic system (SIS) is reported. The fundamental mechanism of sensor‐embedded strain isolation is defined through a combination of analytical and computational studies and validated by dynamic experiments. Comprehensive research of hard‐soft material integration and isolation mechanics provides critical design features to minimize motion artifacts that can occur during both mild and excessive daily activities. A wireless, fully integrated SIS that incorporates a breathable, perforated membrane can measure real‐time, continuous physiological data, including high‐quality ECG, heart rate, respiratory rate, and activities. In vivo demonstration with multiple subjects and simultaneous comparison with commercial devices captures the SIS's outstanding performance, offering real‐world, continuous monitoring of the critical physiological signals with no data loss over eight consecutive hours in daily life, even with exaggerated body movements. 

Abstract Stress is one of the main causes that increase the risk of serious health problems. Recent wearable devices have been used to monitor stress levels via electrodermal activities on the skin. Although many biosensors provide adequate sensing performance, they still rely on uncomfortable, partially flexible systems with rigid electronics. These devices are mounted on either fingers or palms, which hinders a continuous signal monitoring. A fully‐integrated, stretchable, wireless skin‐conformal bioelectronic (referred to as “SKINTRONICS”) is introduced here that integrates soft, multi‐layered, nanomembrane sensors and electronics for continuous and portable stress monitoring in daily life. The all‐in‐one SKINTRONICS is ultrathin, highly soft, and lightweight, which overall offers an ergonomic and conformal lamination on the skin. Stretchable nanomembrane electrodes and a digital temperature sensor enable highly sensitive monitoring of galvanic skin response (GSR) and temperature. A set of comprehensive signal processing, computational modeling, and experimental study provides key aspects of device design, fabrication, and optimal placing location. Simultaneous comparison with two commercial stress monitors captures the enhanced performance of SKINTRONICS in long‐term wearability, minimal noise, and skin compatibility. In vivo demonstration of continuous stress monitoring in daily life reveals the unique capability of the soft device as a real‐world applicable stress monitor.