Mega water control projects constructed in the main river basins in China can be influenced by a lot of uncertainties, such as natural environments, engineering structures and scheduling measures during operation. The benefit of water control projects under the constraint of safety operation is taken as the starting point, risks and opportunities originated from the joint regulation and control of the mega projects made up of cascade water control projects are emphasized. Related research results of water conservancy and hydropower engineering from both home and aboard are compared and the need for scientific research on joint control and safe operation of mega water control projects is proposed. Advances in the mechanisms of safety risk identification, joint operation and multi-objective benefit optimization of mega water control projects are reviewed, based on which a framework for regulation technology systems of mega water control projects is proposed. This paper gives the development direction of the integrated regulation and control technology for mega water control projects considering flood control, power generation, water supply, navigation, ecology, and shipping with multi-dimensional safety.