Most office buildings in the warm-humid sub-Saharan countries experience high cooling load because of the predominant use of sandcrete blocks which are of low thermal mass in construction and extensive use of glazing. Relatively, low night-time temperatures are not harnessed in cooling buildings because office openings remain closed after work hours. An optimization was performed through a sensitivity analysis-based simulation, using the Energy Plus (E+) simulation software to assess the effects of thermal mass, window size, and night ventilation on peak indoor air temperature (PIAT). An experimental system was designed based on the features of the most promising simulation model, constructed and monitored, and the experimental data used to validate the simulation model. The results show that an optimization of thermal mass and window size coupled with activation of night-time ventilation provides a synergistic effect to obtain reduced peak indoor air temperature. An expression that predicts, indoor maximum temperature has been derived for models of various thermal masses.