To better clarify the impact of the integration of education, science and technology, and talent on the cultivation of top-notch innovative talents in universities, this study adopts the fuzzy-set Qualitative Comparative Analysis (fsQCA) method. Using 23 universities in China as the research sample, the findings reveal that: (1) none of the three individual factors, education, science and technology, or talent can independently constitute either a necessary or sufficient condition for high-quality cultivation of top-notch innovative talents; (2) the sufficient condition for achieving high-quality cultivation lies in specific configurations of multiple condition variables; (3) five configurations were identified, from which three distinct paths toward achieving high-quality cultivation were derived. Accordingly, different universities can, based on their own resource endowments and local contexts, select appropriate cultivation paths to effectively enhance the quality of top-notch innovative talent training.