The higher education system of any country is its driving force for socioeconomic development. The research mainly aimed to identify and determine the relationships between the pillars and components of the fourth-generation university in developing countries. The methodology was exploratory mixed-methods (qualitative-quantitative) in terms of data type. The statistical population was composed of academic and organizational experts in the qualitative phase and managers, deputies, administrative staff, and postgraduate students at the Department of Entrepreneurship, Tehran University in the quantitative phase. The participants for the qualitative phase were selected by the purposive (judgmental) method, and the interviews were continued until reaching theoretical saturation, which happened at the 12th interview. The statistical sample size for the quantitative phase was determined to be 273 by Cochran’s formula and the participants were selected by simple randomization. Data were collected through semi-structured interviews and a researcher-designed questionnaire. The validity and reliability were assessed and confirmed for both qualitative and quantitative phases. Data in the qualitative phase were analyzed by content analysis method through the three steps of open, axial, and selective coding using the MAXQDA2020 software package. In the second phase, data were analyzed by confirmatory and exploratory factor analysis using the SmartPLS and SPSS software packages. Based on the results, the factors underpinning the transition of developing countries to the fourth-generation university were studied in four domains of macro-level, intermediate-level, organizational-level, and micro-level factors. Also, the pillars of the fourth-generation university were found to include “responsiveness to society needs”, “entrepreneurship”, “social responsibility”, and “responsive research”.