The transformation of Pearl River Delta (PRD) is characterized by a complex layering, spatial and temporal differentiation. Its complexity is not only caused by interactions between multiple layers like blue-green spatial structure and urban spatial structure, but also caused by the interactions of several large sub-regions that are mutually interrelated. This paper aims to characterise the spatial structure and its evolution as a basis for the development of spatial strategies for future development. In this research, the combination of multiple spatial–temporal approaches and multiple layer approaches for its spatial structure analysis is employed. Firstly, after mapping the evolution process of the PRD, several important sub-regions are analysed. Secondly, evolution mechanism and driving forces are studied in detail. Thirdly, main existing problems are exposed and the causes of these problems are analysed. Finally, several possible strategies for future land-use schemes of PRD are outlined. It is proposed that the land use of future PRD regions should be divided into three spatial zones and four categories of land use. The goals and measures of development for each land-use category are highlighted in order to make contributions to future planning and design.