Emerging classes of flexible electronic sensors as alternatives to conventional rigid sensors offer a powerful set of capabilities for detecting and quantifying physiological and physical signals from human skin in personal healthcare. Unfortunately, the practical applications and commercialization of flexible sensors are generally limited by certain unsatisfactory aspects of their performance, such as biocompatibility, low sensing range, power supply, or single sensory function. This review intends to provide up-to-date literature on wearable devices for smart healthcare. A systematic review is provided, from sensors based on nanomaterials and nanostructures, algorithms, to multifunctional integrated devices with stretchability, self-powered performance, and biocompatibility. Typical electromechanical sensors are investigated with a specific focus on the strategies for constructing high-performance sensors based on nanomaterials and nanostructures. Then, the review emphasizes the importance of tailoring the fabrication techniques in order to improve stretchability, biocompatibility, and self-powered performance. The construction of wearable devices with high integration, high performance, and multi-functionalization for multiparameter healthcare is discussed in depth. Integrating wearable devices with appropriate machine learning algorithms is summarized. After interpretation of the algorithms, intelligent predictions are produced to give instructions or predictions for smart implementations. It is desired that this review will offer guidance for future excellence in flexible wearable sensing technologies and provide insight into commercial wearable sensors.