Some of the greatest human health impacts from infectious diseases are influenced by weather events and seasons, which can shape when and where outbreaks occur, influence the abundance of disease vectors, and affect the survival and transmission of pathogens. Billions are at risk annually from rainfall-dependent malaria, and viral pathogen spillover events and spread of vector-borne diseases (VBD) are increasing due to extreme weather events. In response to these urgent threats, Cornell University has created the Center for Transformative Infectious Disease Research (CTIDR). To have the greatest health impacts, we must change research and practice paradigms from reactive focus on response to outbreaks to proactive understanding of the complex social and environmental conditions that promote risk of outbreaks. We hypothesize that community-engaged research integrating human, reservoir and vector behavior, weather, land-use, human and animal health, and vector/pathogen genomic evolution datasets, will enable creation of predictive epidemiological models and future generation and rigorous testing of preventative interventions. Improved understanding of these relationships will also facilitate current preparation/response. Working toward these goals, we integrate dimensions of building research capacity and performing transdisciplinary research in every element of CTIDR.