The low-oxygen and severe cold climate characteristics of high-altitude regions significantly impact individuals' physiological health and thermal comfort inside buildings, especially for sentry buildings where the enclosure is fully exposed to the outdoors. This study aimed to optimize the indoor environment for high-altitude sentry buildings with attached ventilation. Firstly, the optimal location of exhaust outlets and oxygen sources in the heating mode of high-altitude sentry buildings was studied, and it showed high performance in terms of thermal comfort and energy efficiency. Additionally, the POD method and interpolation methods were applied to expand the sample dataset and identify the optimal combination of attached ventilation parameters and oxygen supply concentration, creating a comfortable, oxygen-enriched environment within the sentry buildings while also considering energy efficiency. The results indicate that when the optimization objective is weighted towards thermal comfort, the percentage of dissatisfied (PD) and the draught rate (DR) values under the optimal scheme are reduced by 82 % and 46.6 %, respectively, compared to previous studies. However, when the emphasis is on energy efficiency in environmental optimization, the air supply energy under the optimal scheme has a 64.4 % reduction compared to previous research results. When considering both optimization objectives simultaneously, the PD and DR values under the optimal scheme are reduced by 35.9 % and 96.9 %, respectively, compared to previous research results. These results demonstrate significant improvements in both thermal comfort and energy efficiency relative to our previous study.