China’s science and technology (S&T) system has experienced significant reform in the Xi Jinping era. This article discusses the evolution, progress, problems and prospects of the reform. For a better understanding of the reform from a holistic perspective, we propose a conceptual framework distinguishing the national S&T system at the macro, meso and micro levels. This article pays particular attention to Xi’s views as guiding principles and the reorganisation of S&T administration at the macro level; the overhaul of the national S&T programmes at the meso level; and the rather ambivalent attitude towards budgeting and spending of funds for S&T projects, and the evaluation system at the micro level. The article also analyses the reform in the Chinese Academy of Sciences as a case study. It concludes with a discussion of the implications of the integration of “top-level design” and the “whole nation system” for the future of China’s S&T enterprise.