A species presence within its geographic range can be influenced by environmental variables and disturbance history, resulting in particular occupancy patterns. Understanding the factors affecting occupancy is essential to evaluate the impact of human activities on species and design conservation or restoration measures. For tropical vertebrates, there is little understanding of how multiple factors influence occupancy and interactions with other species under different conditions and disturbance levels. In this study, we evaluated how natural and human-mediated factors determine the presence of mammals and terrestrial birds in two tropical landscapes that share some species but differ in the type of ecosystems and the degree of human disturbance. We adjusted single-season occupancy models for each species to assess the key variables (human-influenced and natural) determining its presence in each landscape, and co-occurrence models to evaluate potential inter-specific relationships. Although species richness was similar between landscapes, small, generalist species had a higher occupancy in the more disturbed landscape (ψ 0.58 Vs 0.40), while larger species had a higher occupancy in the less disturbed one (ψ 0.79 Vs 0.21). Species in the more fragmented and altered landscape were mainly affected by human-mediated variables, although the effect was not always negative, with smaller species being favored by such conditions. In contrast, in the less altered landscape, environmental variables were more determinant of vertebrate occupancy. Additionally, the number, magnitude, and direction of species interactions usually changed from one landscape to another. Results from this study contribute to the broader understanding of the mechanisms that determine vertebrate occupancy in tropical ecosystems. They confirm how human disturbance can have a direct effect on occupancy of larger species of mammals, and demonstrate how in more altered ecosystems factors associated with human presence may become more limiting or more beneficial than natural ones becoming the primary determinants of occupancy.