Ecosyndemics refer to disease interactions that result from environmental changes commonly caused by humans. In this paper, we push scholarship on ecosyndemics into new territory by using the ecosyndemic framework to compare two case studies—the Southern Interoceanic highway in Peru and the Belo Monte hydroelectric dam in Brazil—to assess the likelihood of socio-environmental factors interacting and leading to ill health in a syndemic fashion. Assessing these two case studies using an ecosyndemic perspective, we find that the construction of dams and highways in tropical forests create the conditions for increases in vector-borne illnesses, surges in sex work and sexually-transmitted infections, and increased psychological stress resulting from violence, delinquency, and the erosion of social cohesion. We suggest that these processes could interact synergistically to increase an individual's immune burden and a population's overall morbidity. However, we find differences in the impacts of the Interoceanic highway and the Belo Monte dam on food, water, and cultural systems, and observed that community and corporate-level actions may bolster health in the face of rapid socio-ecological change. Looking at the case studies together, a complex picture of vulnerability and resilience, risk and opportunity, complicates straight-forward predictions of ecosyndemic interactions resulting from these development projects but highlights the role that the ecosyndemic concept can play in informing health impact assessments and future research. We conclude by proposing a conceptual model of the potential interactions between psychological stress, vector-borne illnesses, and sexaully-transmitted infections and suggest that future investigations of synergistic interactions among these factors draw from the biological, social, and ecological sciences.