Total factor productivity of scientific research is an important index to measure the innovation efficiency of scientific researchers in colleges and universities. The study takes 64 science and technology universities as the research object. Firstly, the data envelopment analysis method is used to determine the six-year mean value of scientific research total factor productivity of 64 science and technology universities, and then the fuzzy set qualitative comparative analysis method (fsQCA) is used to explore the promotion path of scientific research total factor productivity of science and technology universities. It is found that science and technology universities have four paths to improve the total factor productivity of scientific research, and environmental factor, technical factor, human factor, and capital factor can be the core elements of the paths to improve the total factor productivity of scientific research. The research results can provide reference and valuable suggestions for the improvement of scientific research total factor productivity in colleges and universities of science and technology.