Abstract: In the past century, higher education and campus construction have made great progress in China. University campuses and campus buildings, because of their great values in history, culture, and resources, have attracted more and more attention. However, in many cases, there are common problems in existing buildings such as single space forms and pooy adaptability due to construction for specific functions, which can not meet the increasingly diverse needs of eduction and research. Based on long-term effective optimization perspective of campus buildings, taking the southwest building in Gulou Campus of Nanjing University as an example, optimal design of campus buildings was studied in the light of systematic investigation. According to study of optimal design for which the structure system & space layout of existing buildings, as well as optimization and sorting of the relation between "fixed" space and "changeable" space, the long-term effective optimal design of existing campus buildings was realized, with great improvement in the adaptability of buildings, offered campus buildings opportunities to meet not only current needs of faculties and students but also the change of their needs in the future.