The goal of this article is to define the key factors for the development of cross-generational creative teams, the application of which can help businesses achieve maximum use of their human capital and thereby increase their innovative potential. The need to explore this issue is due not only to technical and technological development, which is fundamentally changing the content of work and the approach to work, but also due to the current lack of workers on the labor market of the Czech Republic and other EU countries. Findings from this article are based on a quantitative study on the research sample of 341 SMEs from the EU for the period 2017–2019. The data examined were obtained based on a personalized questionnaire in the SMEs. The outputs of the key factors for innovation potential of cross-generational creative teams’ linear correlation were further validated by experimental testing on a selected set of successful creative teams. During this testing in the form of in-depth semi-structured interviews, key areas of human resource management were defined in order to achieve more efficient use of human capital. It was confirmed that cross-generational creative teams have an influence on the innovative planning or financial health of a company, and four key areas of HR management were defined to increase the innovation potential of human capital: care and motivation of existing creative team members; acquisition of new creative team members; defining the competencies of creative team members; communication and digital culture.