The general objective of the study is to establish the determinants that stimulate knowledge transfer (KT) between university-industry (U-I) actors within the Regional Innovation Systems (RIS); it has a mixed approach, descriptive and explanatory type, preceded by exploratory inquiry using Boolean equations, in addition to documentary review techniques, in-depth interviews, surveys, and case studies, an exploratory and confirmatory principal component analysis is carried out, cited as appropriate in the scientific documents reviewed. It is novel that studies are carried out more frequently in regions, mainly Europe, Asia, and North America. There are antecedents in Latin America and Colombia with other scopes. Once the categories and factors of KT and RIS have been defined, with the survey results, the "KT-RIS model" is proposed, encompassing 60 indicators. Then the dynamics of the system in Stella (software) are elaborated, indicating that the flow of the knowledge generation subsystem (SubGen) is at 2.1/5 (42%) for KT and the flow of the application subsystem (SubApp) is at.6/5 (12%), that is, 28.59% of what is generated in the case study university (barriers) is absorbed. Applying Solver optimization methods, it is found that SubGen can generate up to 3.5/5 of knowledge, and industries could absorb a maximum of1.6 of that SubGen flow through enhancers.