This paper experimentally demonstrates a crossed reaction of pure and hybrid graphene oxide (GO)/tantalum dioxide (TaO2) as a volatile organic compound (VOC) absorber in a guided mode resonance (GMR) sensing platform. The proposed GMR platform has a porous TaO2film as the main guiding layer, allowing for more molecular adsorption and enhanced sensitivity. GO is applied on top as an additional VOC absorber to increase the selectivity. The hybrid sensing mechanism is introduced by varying the concentration of the GO aqueous solution. The experimental results show that the pure TaO2-GMR has a high tendency to adsorb most of the tested VOC molecules, with the resonance wavelength shifting accordingly to the physical properties of the VOCs (molecular weight, vapor pressure, etc). The largest signal appears in the large molecule such as toluene, and its sensitivity is gradually reduced in the hybrid sensors. At the optimum GO concentration of 3 mg/mL, the hybrid GO/TaO2-GMR is more sensitive to methanol, while the pure GO sensor coated with GO at 5 mg/mL is highly selective to ammonia. The sensing mechanisms are verified using the Density Functional Theory (DFT) to simulate the molecular absorption, along with the measured functional groups measured on the sensor surface by the Fourier transform infrared spectroscopy (FTIR). The crossed reaction of these sensors is further analyzed by means of machine learning, specifically the principal component analysis (PCA) method and decision tree algorithm. The results show that this sensor is a promising candidate for quantitative and qualitative VOCs detection in sensor array platform.