Wearable devices represent a versatile technology in the IoT paradigm, enabling non-invasive and accurate data collection directly from the human body. This paper describes the development of a smart shirt to monitor working conditions in particularly dangerous workplaces. The wearable device integrates a wide set of sensors to locally acquire the user’s vital signs (e.g., heart rate, blood oxygenation, and temperature) and environmental parameters (e.g., the concentration of dangerous gas species and oxygen level). Electrochemical gas-monitoring modules were designed and integrated into the garment for acquiring the concentrations of CO, O2, CH2O, and H2S. The acquired data are wirelessly sent to a cloud platform (IBM Cloud), where they are displayed, processed, and stored. A mobile application was deployed to gather data from the wearable devices and forward them toward the cloud application, enabling the system to operate in areas where a WiFi hotspot is not available. Additionally, the smart shirt comprises a multisource harvesting section to scavenge energy from light, body heat, and limb movements. Indeed, the wearable device integrates several harvesters (thin-film solar panels, thermoelectric generators (TEGs), and piezoelectric transducers), a low-power conditioning section, and a 380 mAh LiPo battery to accumulate the recovered charge. Field tests indicated that the harvesting section could provide up to 216 mW mean power, fully covering the power requirements (P¯ = 1.86 mW) of the sensing, processing, and communication sections in all considered conditions (3.54 mW in the worst-case scenario). However, the 380 mAh LiPo battery guarantees about a 16-day lifetime in the complete absence of energy contributions from the harvesting section.