In Taihu Basin, China’s first trans-boundary regional lake chief cooperation mechanism has been established. The trans-boundary governance problem of the basin is a typical regional overall management problem, and it is also a significant point for the balanced development of social economy and ecological environment within the administrative scope of the basin. The improvement of trans-boundary lake chief system is an important guarantee for the social development and construction within the basin. The intrinsic mechanism is studied through the attribution analysis of the multi-player game between lake chief and enterprises, intra-regional lake chief and inter-regional lake chief to the governance dilemma of Taihu Lake. It is found that the internal cause of the problems of the lake chief system in Taihu Basin lies in the interest correlation of rational economic man, and a win-win situation can be achieved through external elements. By referring to matrix organization framework and integrating the hierarchical system of lake chiefs and the synergy theory of each region in the basin, a multi-dimensional framework of regional collaborative governance in Taihu Basin is constructed. It includes the multi-dimensional role of multiple subjects of “government + enterprise + social organization + public”. Based on the framework of regional collaborative governance, the following suggestions and conclusions are put forward. From the perspective of the government, the division of power and responsibility should be clarified to improve the evaluation system. From the perspective of enterprises, ecological compensation should be optimized, and technological innovation should be strengthened. From the perspective of social organization, more scientific research joint projects should be carried out, and theoretical penetration should be strengthened. From the point of view of the public, more people are encouraged to participate in governance, and the feedback effect should be strengthened.