The third millennium marks the opening of a new historical cycle for university education, the new Venezuelan university, which stands in the context of the Mission Alma Mater, based on a new conception of society, science and technology and professional is required for national and Latin American integration. This third historical cycle of the university consists of momentous changes not only in the fundamentals and principles that define the phenomenology university, but also how these have operated for so long. Therefore arises as the central axis of the article, the need for a new epistemological conception of the university. This paper presents new definitions and ways of responding to this epistemological void, specifically in the transformation of the Colleges and University Institutes of Technology in Regional Polytechnic Universities, a process that is part of the Mission Alma Mater, which constitutes the axis central to the expansion and modernization of the education system and one of the biggest challenges of the Bolivarian government for Venezuela's college education.