Water circumnavigates the Amazon River Basin’s urban centers, blurring lines between city and river. As Amazonian cities swell, growing populations inhabit the seasonally flooding edges of the urban landscape. These amphibious communities, which are adapted to both high and low river seasons, are often informal and are disproportionately vulnerable to health risks tied to socioeconomic inequality, climate change, and urban systems. Though Indigenous architecture has designed with Amazonian hydrology for millennia, colonial ideas of the form that urbanization should take eschew amphibiousness. This design research focuses on the amphibious informal community of Claverito, in Iquitos, Peru to examine the built environment as a social determinant of health and to ask: What is the role of evidence-based ecological design in informal community upgrading? How can health data center people in informal community redevelopment to align with the UN Sustainable Development Goals? How can a landscape systems approach to built environment design mitigate risk of exposure to water-related infectious diseases while contributing to city-wide resilience?