Ocimum basilicumvar.thyrsiflorais valuable for its medicinal properties. The barriers to the commercialization of essential oil are the lack of requisite high oil-containing genotypes and variations in the quantity and quality of essential oils in different geographic areas. Thai basil’s essential oil content is significantly influenced by soil and environmental factors. To optimize and predict the essential oil yield of Thai basil in various agroclimatic regions, the current study was conducted. The 93 datasets used to construct the model were collected from samples taken across 10 different agroclimatic regions of Odisha. Climate variables, soil parameters, and oil content were used to train the Artificial Neural Network (ANN) model. The outcome showed that a multilayer feed-forward neural network with an R squared value of 0.95 was the most suitable model. To understand how the variables interact and to determine the optimum value of each variable for the greatest response, the response surface curves were plotted. Garson’s algorithm was used to discover the influential predictors. Soil potassium content was found to have a very strong influence on responses, followed by maximum relative humidity and average rainfall, respectively. The study reveals that by adjusting the changeable parameters for high commercial significance, the ANN-based prediction model with the response surface methodology technique is a new and promising way to estimate the oil yield at a new site and maximize the essential oil yield at a particular region. To our knowledge, this is the first report on an ANN-based prediction model forOcimum basilicumvar.thyrsiflora.