This paper proposes the indicator systems and integrated desirability framework for comprehensive evaluation towards the operating speeds of high-speed railway (HSR). Speed is a crucial piece in the characterization of the HSR system. The debate about what is the most appropriate operating speed continues. The established indicator systems and integrated desirability framework can comprehensively evaluate the HSR operating speeds from stand points of the economic efficiency, operational efficiency, track capacity, operational security, and environment impact. Moreover, the integrated desirability framework, which is a combination of entropy-analytical hierarchy procedure (EAHP) and technique for order preference by similarity to ideal solution (TOPSIS), can output some references for selecting the most suitable speed regimes of HSR. The application of the desirability framework to the case of China high-speed railway (CHSR) is demonstrated concretely. Based on the case study of CHSR, the comprehensive analysis of the effectiveness of the indicator systems on HSR operating speeds is carried out. The case study shows that the proposed indicator systems and integrated desirability framework can be used to evaluate comprehensively the HSR operating speeds under various conditions.