We report a single-step hydrothermal synthesis of morphologically engineered biomimetic three-dimensional (3D) biconcave-shaped Bi2WO6-nanostructures for photo-enhanced ultrasensitive determination of nicotine in human sweat and cigarette samples. Detailed characterization reveals the formation of orthorhombic, red blood cell-mimicking Bi2WO6 nanoparticles. The average diameter of the biconcave Bi2WO6 nanoparticles ranged from 50 to 100 nm. The fabricated sensor displayed a sensitivity of 56.97 ± 2 μM-1 in the wide linear range of 50 nM-100 μM, with a limit of detection (LOD) of 13 nM (3σ) when exposed to nicotine. An enhanced sensitivity of 83.23 ± 1 μM-1 and a reduced LOD of 0.9 nM in the presence of UV light can be attributed to the outstanding sensing response of nicotine in the presence of UV light due to the synergistic-catalytic and photo-responsive properties of large-surface-area Bi2WO6 nanostructures. The photoinduced oxygen ions react with the adsorbed oxygen atoms assisting in the formation of O2- ions, which further contributes to the enhanced interaction with nicotine. The sensor displayed excellent selectivity toward nicotine in the presence of interferences and was robust to bending conditions, thus bolstering its practical applicability. Further, the sensor was employed in determining the unknown concentrations of nicotine in sweat and commercially available cigarettes. The strategy employed here expands the scope of photo-activated flexible nanoelectronic devices to develop affordable platforms for sensing various bioanalytes. © 2020 American Chemical Society.