The construction of modern canals is the key task of constructing a national comprehensive three-dimensional transportation network in the future. It has extremely important strategic significance in inland navigation. This paper focuses on the theme of “Efficient and Safe Operation of Green Waterways for Modern Canals”, reviews the major challenges of water ecological security and efficient and safe operation of waterways in the construction of modern canal projects, and analyzes relevant research progress. Furthermore, it summarizes five urgent scientific issues, including the ecological response mechanism of the corridor habitat of large-scale canal projects, the canal ecological regulation mechanism integrating water quality, habitat, and landscape, the multi-physical process and regulation mechanism of high-density ship movement and saltwater intrusion, the complex hydrodynamic coupling mechanism and navigation safety regulation of the waterway between locks, and the formation mechanism of complex flow patterns at the intersection of stem stream and tributaries and the navigation safety guarantee mechanism. It will help realize the construction of a green and low-carbon modern canal project and provide scientific and technological support for the high-quality construction of the national comprehensive three-dimensional transportation network.