The Neotropics realm is a significant biogeographic region in tropical and subtropical areas of the Americas, with high biodiversity and endemism. This region serves as a prime example of how genetics and ecology intersect, especially when considering that genetic diversity in this region plays a crucial role in shaping ecological processes and species interactions. The genetic makeup of species within the Neotropics also influences their ecological roles and functions: genetic variation can affect traits such as reproductive strategies and physiological adaptations, which in turn influence the ecological relationships and species interactions. The intricate relation between genetics and ecology highlights the importance of preserving both the genetic diversity and the ecological integrity of the landscape. Fortunately, with all the data available on the Neotropics, computational approaches such as ecological niche modeling (ENM) can be used to uncover insights into how environmental factors and historical events have influenced the distribution of populations and their genetic diversity, especially under climate change scenarios. ENM provides means for identifying barriers to gene flow, areas of historical isolation, and test biogeographical hypotheses on how environmental factors have affected the genetic diversity of populations. This chapter is aimed at introducing the core concepts of ecological niche models, their intersection with population genetics studies, and applications of ENMs in conservation efforts and biodiversity management studies in the Neotropics to ensure the long-term viability and sustainability of the neotropical ecosystems in the face of human interference and environmental challenges.