This paper reports on the findings of an experimental study that investigated the impact of various environmental factors on the growth of lettuce and basil plants in vertical farms. The study employed the Taguchi method, a statistical design of experiments approach, to efficiently identify the optimal growth conditions for these crops in a hyper-controlled environment. By reducing the time and cost of designing and running experiments, this method allowed for the simultaneous investigation of multiple environmental factors that affect plant growth. A total of 27 treatments were selected using the Taguchi approach, and the signal to noise ratio was calculated to predict the optimal levels of each environmental condition for maximizing basil and lettuce growth parameters. The results showed that most of the parameters, except for EC and relative humidity for certain growth parameters, were interrelated with each other. To validate the results, confirmation tests were conducted based on the predicted optimal parameters. The low error ratio between expected and predicted values (1–3%) confirmed the effectiveness of the Taguchi approach for determining the optimal environmental conditions for plant growth in vertical farms.