Multifunctional wearable systems and sensors have attracted much interest in recent years because they can monitor multiple physical, environmental, and physiological parameters simultaneously, facilitating real-time health monitoring, environmental monitoring, and smart system integration. Advances in materials science, sensor structure, and manufacturing processes have resulted in the creation of miniaturized, flexible, and robust sensors to sense temperature, pressure, strain, humidity, light, gas, and acceleration—frequently in a single device. These sensors take advantage of novel materials, like low-dimensional nanostructures and upconverting nanoparticles, and new integration schemes like planar, 3D, and stacked structures. In addition, the integration of sensor fusion, energy harvesting, and information storage capability in multifunctional platforms gives rise to new opportunities for wearable electronics, human–machine interfaces, and Internet of Things (IoT) applications. In spite of fault tolerance and long-term reliability challenges, ongoing design optimization and innovative fabrication technologies are propelling the field toward more flexible, capable, and affordable multifunctional sensing solutions.