In the era of globalization, key production factors such as population, industry, energy, and trade are flowing rapidly across regions. The relationship between human and environment has changed from a static to a dynamic status, from isolation to networking, and the geographical scale has been fully enlarged, indicating the transformation of human-land relationship from regional to global scale. As the frontiers of China’s opening up, the Guangdong-Hong Kong-Macao Greater Bay Area has undergone profound changes in its man-land relationship in the past 40 years of reform and openning-up. It is of great theoretical and practical significance to re-recognize, study and adjust the global and local modes of the man-land relationship in the study area, so as to provide information on how the bay area can rationally allocate the core elements on global and regional scales and develop into a world-class bay area. This paper reviews the global transformation of man-land relationship in the new era, and prospects the study of man-land relationship in the Guangdong-Hong Kong-Macao Greater Bay Area. It aims to: (1) examine the general man-land relationship patterns and laws of the world-class bay area from regional to global in theory; (2) analyze the global allocation process and changing influencing factors of man-land relationship in the Greater Bay Area since the reform and opening-up in the late 1970s; (3) reveal the local response and regional system mechanism within the bay area based on the global model; (4) explore the path of reconstruction of the “innovation-industry-environment” key system; (5) propose the optimization and regulation pathways of the man-land relationship in the region in the new era.