Stratum ventilation with proper operation can energy-efficiently provide thermal comfort and good quality of inhaled air. Previous studies were mainly focused on stratum ventilation for cooling, with little attention on stratum ventilation for heating. Proper operation of stratum ventilation for heating is more complicated, with multiple ventilation operation parameters (i.e., the supply vane angle, supply airflow rate, and supply air temperature) non-linearly affecting multiple mutually conflicting criteria of the ventilation performance (i.e., thermal comfort, air quality, and energy efficiency). In this study, the operation of stratum ventilation for heating is optimized by using a multi-criteria decision-making technology, namely a technique of order preference by similarity to ideal solution (TOPSIS). An experiment on stratum ventilation for heating a typical office is conducted. Based on experimentally validated Computational Fluid Dynamics (CFD) simulations, response surface models of the ventilation performance are developed to promote the computational efficiency of the TOPSIS optimization. The operation optimization on the ventilation parameters significantly improves the ventilation performance, with an average reduction of 16.3% and 29.5% in the Predicted Percentage Dissatisfied and the local mean age of air, respectively, and an average increase of 7.0% in the energy utilization coefficient. When the outdoor weather varies, the optimal supply air temperature varies most frequently with the greatest variation range, followed by the optimal supply vane angle, and the optimal supply airflow rate. With the ability to modulate the optimal supply air temperature as a response to outdoor-weather variations, the constant-air volume system is preferable to the variable-air-volume system.