Since the new century, the need for building the National Innovation System(NIS) in Cambodia has emerged gradually. And the need for industrial structural transformation and the lack of technological innovation have proposed new requirements to higher education. Talents, knowledge and cooperation are the three core elements of university-NIS engagement. Following this logic, Cambodian universities play the roles of quality human resource concentrator, knowledge producer and social engine to contribute to the whole NIS. In general, the innovation-driven development of Cambodian universities still face tons of challenges, such as lack of resources, institutional obstacles and unfavorable environment.