Fruits and vegetables have shorter shelf life due to their perishable nature. Tomato, being a nutritionally rich fruit needs to be preserved for a longer period. In this context, this study was designed to dry the tomato slices through microwave–vacuum drying. This process was optimized for moisture ratio and drying rate using response surface methodology (RSM). The process was investigated at different power levels (30, 50, 80, and 100 W), pressure (0, 15, 20, and 25 inHg), and time (0, 4, 6, and 10 min) using Box–Behnken design. Results indicated that color, energy efficiency, and drying characteristics were significantly affected by changing power, vacuum levels, and processing time. Besides, nine mathematical models were applied on experimental data to deeply understand the moisture ratio of tomato slices. Amongst, Midilli model was found best to describe the drying process at 100 W and 25 inHg supported by R2 (0.9989), RMSE (0.001), and X2 (1.34e−4). This study was focused on finding the optimal combinations of power, vacuum pressure, and time for better drying and reduced wastage of the fruit owing to its perishable nature. From all the microwave powers, higher microwave power and vacuum level showed better energy consumption, energy efficiencies, color retention, and rehydration capacity.