With uncertainty intensifying the international technological innovation environment, the innovation situation of Chinese manufacturing enterprises has been impacted. Based on 12,781 micro panel data in 2011–2020 of 2347 Chinese A-share manufacturing listed enterprises, this paper empirically analyzes the impact of innovation plight faced by enterprises on operational efficiency. The innovation plight in this article refers to the degree to which the actual innovation performance of enterprises has not reached the expected innovation performance or is introduced by an innovation gap, measured by the difference when actual innovation performance is lower than the expected innovation performance. The empirical results show that the innovation plight of manufacturing enterprises significantly inhibits operational efficiency by reducing their risk tolerance, development ability expectation, and profitability. After using a series of tests, such as the instrumental variable method, replacing the dependent variable, and changing the parameters for measuring the independent variable, the conclusion is still robust. In addition, the results illustrate that the inhibitory effect of innovation plight on operational efficiency is more obvious for non-state-owned enterprises, small and medium-sized enterprises, high-tech enterprises, and enterprises in the eastern region. Finally, we formulate some relevant management suggestions.