After the ‘unipolar moment’ of the 1990s, the emerging multipolar world order has brought a new environment for regional organisations, which they are adjusting to. Mercosur and Visegrad Group, with semi-peripheral member states, are both categorised as intermediate regions with close institutionalised and cultural links to the Western world, while structural political and economic features distinguish them from the core regions. Carrying out a comparative analysis, the article’s research question is: How have leadership, objectives and actorness changed in the case of Mercosur and Visegrad Group since 2000 as a response to the changing world order? A case study analysis explains the similarities and differences between Mercosur’s and Visegrad Group’s responses to and performance in the changing world order. Criticisms towards the traditional partners, shifting agendas, a search for alternatives beyond the Western model of market democracy and building links with emerging partners are the most essential similarities of Mercosur’s and Visegrad Group’s responses.