According to a guideline published by the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), people spend 80%–90% of their lives indoors; therefore, managing indoor environmental quality is becoming increasingly significant. In particular, a very high level of indoor CO2 concentration can seriously impair people’s comfort, health, and productivity. The ASHRAE recommends maintaining indoor CO2 concentration below 1,000 ppm. This study proposes a novel integrated approach to evaluating the effect of indoor CO2 concentration on human cognitive performance and neural responses in office environments from multiple perspectives. An integrated performance score (IPS) w developed to investigate objectively and comprehensively how indoor CO2 concentration affects the level of cognitive performance compared with the neural responses of the subjects, in which the brain regions were considered along with the brain-wave frequency bands. Thirty participants were asked to engage in nine (three×three) experiments, i.e., three cognitive tasks (i.e., working memory, mental workload, and visual concentration) under three CO2 concentration levels (i.e., a low CO2 level of 500 ppm; a moderate CO2 level of 1,000 ppm; and a high CO2 level of 2,500 ppm). During the experiments, electroencephalography (EEG) signals were recorded. Compared with the individual approach, the integrated approach can explain more clearly that an increase in indoor CO2 concentration had a detrimental effect upon working memory, mental workload, and visual concentration. The study breaks new ground in applying a biometric research strategy in the domain of management in engineering, using EEG-based integrated performance assessment. This study can contribute to properly designing the space size and the number of occupants during space programming. In addition, it can be used for optimally designing and operating ventilation systems at proper size and with proper strategy. Consequently, it is expected that the negative effect of indoor CO2 concentration on occupants can be minimized.