This study provides insights into the challenges involved in predicting the Reid vapor pressure (RVP) of gasoline-oxygenate blends (GOB), which is an important indicator of fuel quality and compliance with environmental and performance standards. Given the enormous variety of gasoline compositions and ratios available, there is a significant demand for a fast, straightforward, and cost-effective technique to predict RVP without relying on costly instruments or complicated spectral measurements that involve numerous input variables. A comparative performance analysis has been performed for different regression modelling strategies for predicting RVP in GOB, which is valuable for researchers and practitioners in the petroleum industry for saving time and money. Parametric and nonparametric approaches were compared using partial least squares regression (PLSR), nonlinear regression (NLR), and nonparametric regression (NPR) models. Locally weighted scatterplot smoothing (LOWESS) approach was applied to the NPR model. The gasoline’s physical characteristics (distillation curves and density) formed the basis for the analysis of these models’ performances. Acceptable error metrics have been reached for root mean square error of calibration and prediction (RMSEC and RMSEP) values, for the PLSR, NLR, and NPR models, which are 4.790, 6.235, 4.739, 6.149, 3.968, and 6.029, respectively, which are close for those reported in literature. The NPR model eliminates parametric constraints and allows for a different kind of data structure to emerge. The established models here demonstrate a sound ability to overcome barriers by omitting the use of inconvenient spectral measurements to save expense and simplify data calibration, making them a promising approach for RVP detection of GOB. This finding aids in the development of more accurate RVP prediction models and contributes to the optimization of fuel formulations.