Background: Recent studies have highlighted the significant impact of combined thermal and lighting conditions on human comfort. However, there is limited understanding of how these factors influence cognitive performance in older adults. This study explored the effects of complex thermal and lighting conditions on various cognitive functions and physiological responses in older adults. Additionally, a predictive cognitive model was developed using physiological indicators as well as demographic factors. Methods: Twenty-two older adults participated in a within-subject design experiment under different thermal and lighting combinations. The study focused on two temperature conditions, 18 °C and 28 °C, and two lighting conditions, 480 nm with 5500 K and 644 nm with 3200 K. Conclusions: The finding showed that males significantly performed better at 18 °C under 480 nm lighting, while females excelled at 28 °C under 644 nm lighting. Electrodermal activity (EDA) increased in warmer conditions with warmer lighting, and pupil size expanded similarly but decreased under cooler conditions. Males’ EDA was negatively correlated with cognitive performance, while females’ pupil size and BMI were positively correlated. Using the classification and regression tree (CART) algorithm, predictive model demonstrated 89.7% accuracy. These findings emphasize the potential of optimizing thermal and lighting conditions to enhance cognitive functions and predict performance in older adults