The paper provides a comparative analysis of the presidential systems of Argentina, Colombia, Chile, and Uruguay, covering the period between 1989 and 2022, with the aim of examining the factors that motivate a person in the head of a ministry to seek the presidential candidacy. The central argument holds that both the incumbent president and the political parties have the purpose of taking advantage of a person’s passage through a Cabinet of State to boost his or her presidential candidacy within the political organization. The selected cases are justified due to the existence of historical moments in which ministers have left their posts to compete for the presidency in these countries. The methodology employed in this study follows a multi-method logic. First, quantitative logistic regression analysis is used, followed by qualitative press analysis of ministers’ careers to support the theoretical argument. The most notable results highlight that having a political profile, being a member of the president’s political party and having held a political ministry are influential factors when running in presidential elections.