In the present work, the effects of different operating parameters on the performance of a gravity-assisted heat pipe-based indirect evaporative cooler (GAHP-based IEC) were investigated. The aim of the theoretical study is to evaluate accurately the cooling performance indicators, such as the coefficient of performance (COP), wet bulb effectiveness, and cooling capacity. To predict the effectiveness of the air cooler under a variety of conditions, the comprehensive calculation method was adopted. A mathematical model was developed to simulate numerically the heat and mass transfer processes. The mathematical model was validated adequately using experimental data from the literature. Based on the conducted numerical simulations, the most favorable ranges of operating conditions for the GAHP-based IEC were established. Moreover, the conducted studies could contribute to the further development of novel evaporative cooling systems employing gravity-assisted heat pipes as efficient equipment for transferring heat.