National scientific research projects with high uncertainty should pay more attention to the realization of technological innovation management. The past linear performance management system only can realize the performance optimization of the project itself. But the lagging is strong, the strain is big, the project management urgently needs the dynamic management transformation. Based on the in-depth deconstruction of the high-uncertainty attributes of national scientific research projects, through the theoretically analysis of the management practice of the new drug research and development in the major science and technology projects, the uncertainty model is built from three perspectives: time, process, and output. By drawing lessons from domestic and foreign project management practices, suggestions are provided from two aspects, theoretical reform and organizational optimization to realize the dynamic management of national scientific research projects under the new management trend.