The effective allocation of internal resources in manufacturing enterprises is an inherent problem related to the effectiveness of transformation and upgrading, in which how the configuration of resource allocation affected has not been fully studied. This paper divided the resource or condition elements of an enterprise into four aspects: R&D investment, manpower level, development potential and customer concentration. The enterprise size was set as the regulating variable, and the fuzzy set qualitative comparative analysis method was used to analyze and study the effective configuration of resource allocation in the context of enterprise transformation and upgrading. Through the case study of 31 manufacturing enterprises, four effective configuration forms of resource allocation were obtained: high risk-resistant resource allocation configuration, high innovation input resource allocation configuration, high market position resource allocation configuration and close customer relationship resource allocation configuration. The research conclusion confirmed the objective existence of the resource allocation configuration effect of transformation and upgrading, which will not only enrich the theory and method of an enterprise’ transformation and upgrading, but also provide enlightenment for the path choice and effectiveness analysis on the enterprises’ transformation and upgrading.