Driving is a ubiquitous activity that requires both motor skills and cognitive focus. These aspects become more problematic for some seniors, who have underlining medical conditions and tend to lose some of these capabilities. Therefore, driving can be used as a controlled environment for the frequent, non-intrusive monitoring of bio-physical and cognitive status within drivers. Such information can then be utilized for enhanced assistive vehicle controls and/or driver health monitoring. In this paper, we present a novel multi-modal smart steering sleeve (S3) system with an integrated sensing platform that can non-intrusively and continuously measure a driver’s physiological signals, including electrodermal activity (EDA), electromyography (EMG), and hand pressure. The sensor suite was developed by combining low-cost interdigitated electrodes with a piezoresistive force sensor on a single, flexible polymer substrate. Comprehensive characterizations on the sensing modalities were performed with promising results demonstrated. The sweat-sensing unit (SSU) for EDA monitoring works under a 100 Hz alternative current (AC) source. The EMG signal acquired by the EMG-sensing unit (EMGSU) was amplified to within 5 V. The force-sensing unit (FSU) for hand pressure detection has a range of 25 N. This flexible sensor was mounted on an off-the-shelf steering wheel sleeve, making it an add-on system that can be installed on any existing vehicles for convenient and wide-coverage driver monitoring. A cloud-based communication scheme was developed for the ease of data collection and analysis. Sensing platform development, performance, and limitations, as well as other potential applications, are discussed in detail in this paper.