With the advent of the Internet of Things (IoT), strong demand has grown for flexible and wearable sensors. Particularly, sensors based on small organic molecules and polymers have recently attracted great interest due to their high potential for use in flexible, low-cost, solution-processable, large-area electronics. Functional properties of organic and polymeric active layers can be tailored by rational molecular design or surface functionalization to enhance their selectivity and sensitivity. Nanoscopically engineered organic and polymeric semiconducting materials have emerged as promising building blocks for high-performance flexible sensors. In this talk, the development of high-performance organic and polymeric semiconductors will be presented with viable approaches to selectively tune the dominant polarity of charge carriers and achieve efficient charge transport, which embrace the rational design of conjugated backbones, side-chain engineering, microstructural and morphological control. Unconventional organic and polymeric nanomaterials covering single-crystalline nanowires, nanoporous films, core-shell nanomaterials, multiple-patterned plasmonic nanostructures, and chiral supramolecules will be described with their applications in flexible and wearable sensors including photodetectors, chemical and biological sensors. In addition, the fundamental charge transport and photophysical phenomena of molecule-based active layers will be discussed.