A catalyst active to carbon monoxide (CO) oxidation at low temperature is essential for environmental conservation, saving fuel and improvement of the quality of human life. Rational design of CO oxidation catalyst on the basis of comprehensive understanding of physicochemical properties of catalytic materials, rather than simply searching for the catalyst based on trial‐and‐error, is a promising approach to meet the increasingly stringent regulations. This review covers metal‐doped and ‐loaded system based on CeO2 catalysts as strategies to significantly improve CO oxidation activity at low temperature. When incorporated into CeO2 lattice, active metals significantly lower the oxygen vacancy formation energy (Evf) of the catalyst surface, resulting in high catalytic activities at low temperature. When the active metals are loaded on the CeO2 surface, many active sites could be acquired by increasing the dispersion, and the catalytic activity can be dramatically improved by newly introducing the interfacial sites between the metals and the CeO2 support. Doping the support could further improve this loaded system in terms of specific surface area, oxygen vacancy formation, and spillover effects. In this review, based on this knowledge, we propose a rational design approach to a robust low‐temperature CO oxidation catalysts. The desirable CO oxidation catalysts identified from the interplay between theoretical and experimental approaches would ultimately improve the quality of human life, and create potential economic benefits by alleviating air pollution.