PurposeAdopting more sustainable and social-oriented perspectives is crucial for the emergence of the so-called humane entrepreneurial ecosystems (HEEs), the last ones supporting the improvement of both economic, environmental and social wealth. Entrepreneurs act as keystone players in each entrepreneurial ecosystem, thus the emergence of Humane Entrepreneurship (HumEnt) is crucial in shaping HEEs. Given the role of culture in affecting HumEnt, the relationships between Humane Orientation (HO) – as defined in the GLOBE project – and the basic components of Humane Entrepreneurship (HumEnt) were, particularly, explored in a selected sample of countries. Both Intellectual Capital (IC) and knowledge management (KM) perspectives were adopted in pursuing the research goal.Design/methodology/approachThe study approaches this by the mean of the Ward method with Euclidean squared distance and the k-means method. The GLOBE project, the Global Entrepreneurship Monitor (GEM), the Environmental Performance Index (EPI) and the International Social Survey Program (ISSP) were used as data sources. Correlations between HO “as is” scores and each components of HumEnt were checked for the world sample (N = 36), as well as for the groups of innovation-driven countries (N = 17) and European countries (N = 14).FindingsResearch results show a conditional confirmation of the developed hypotheses, depending on countries cultural levels of HO, with a moderating role exercised by the economic development on the relationship between culture and HumEnt.Originality/valueGiven the increasing pressure of fundamental societal challenges, such as climate change, poverty and increasing inequality within and between countries intensified by pandemic (UN report, 2021), integrating the more traditional approaches to profit seeking with the more sustainable and human-centric perspective is a priority for both scholars and society at large. Previous researches do not provide explanation about the contextual factors responsible for the emergence of more humane-oriented entrepreneurial ecosystems, especially when referring to culture. This article broadens our understanding about the reason why both HumEntr and HEEs differently arise and develop in different cultural contexts.