A spatio-temporal model of megacity development that treats the megacity as an active medium is presented. From our point of view, it is advisable to consider the process of urban ecosystem development from the standpoint of the theory of autowave self-organization in active media. According to this concept, the urban ecosystem is considered as interacting with each other’s natural and anthropogenic subsystems with significant heterogeneity of areas affected by human intervention and urban geobiocoenoses. The model is based on the general principles of active medium dynamics; therefore, it is universal for any object to be considered an active medium. The only difference when using the model to predict the development of urban ecosystems in countries with different socio-economic and political prerequisites is the variety of parameters included in the model, i.e., the activation parameter, the autowave process inhibitors, and the characteristic scales of the activator and inhibitor. The model was tested on the example of Moscow expansion in the period of 1952–1968 and showed good agreement with the map data. By means of the model, a prediction of Shanghai and surrounding territory development until 2030 was made.