Global response to climate-sensitive infectious diseases has been uncertain and slow. The understanding of the underlying vulnerabilities which forms part of changes created by forces within the Earth system has never before been critical until the coronavirus disease 2019, “COVID-19” pandemic with the initial developmental phase linked to weather elements and climate change. Hence, the heightened interest in climate-sensitive infectious diseases and GeoHealth, evident in the renewed calls for “One Health” approach to disease management. “One Health” explains the commonality of human and animal medicine, and links to the bio-geophysical environment, yet are at crossroads with how forces within the Earth system shape etiologies, incidences, and transmission dynamics of infectious diseases. Hence, the paper explores how these forces, which are multistage and driven by climate change impacts on ecosystems affect emerging infectious diseases, leading to the question “what drive the drivers of diseases?” Three questions that challenge broad theories of Earth system science on boundaries and connectivity emerged to guide study designs to further interrogating disease surveillance and health early warning systems. This is because, climate change (a) drives prevailing biological health hazards as part of forces within the Earth system, (b) shifts disease control services of ecosystems and functioning to effectively regulate disease incidence, and (c) modifies pathogen—species hosts relationships. Hence, the need to rethink pluralistic concepts of climate-sensitive diseases in their infection and management from a GeoHealth perspective, which “One Health” potentially conveys, and to also maintain ecosystem health.