In this study, we designed efficient nanobiosensors based on two-dimensional tungsten diselenide (WSe2) monolayers to detect specific volatile organic compounds (VOCs) related to depression, such as butyric acid, furan, N-butylamine, and trimethylamine. First-principles calculations based on density functional theory revealed weak adsorption energies (Eads) on pristine (WSe2) and single Se-vacancy-induced (VSe−WSe2) monolayers. However, doping single atoms of Co, Fe, and Ni in WSe2 at small concentrations of 1.33% not only improved the Eads values but also altered the electronic structures, which are essential for efficient sensing applications. Among the doped systems, Fe@ WSe2 showed tremendous improvement in its adsorption mechanism. Bader charge analysis, electrostatic potential, and work function calculations further validated the VOC sensing capabilities of the single-atom-dispersed WSe2 monolayers. Additionally, the detection of VOCs under varying temperature and pressure conditions was investigated by using statistical thermodynamic analysis based on the Langmuir adsorption model.