In Kilombero district, in South-central Tanzania, rapidly evolving environmental conditions, land-use transformations and conservation policies are restructuring human-rodent interactions including epizootics. This article examines how these changes shape the local epistemologies of health and coexistence. While biomedical discourses frame rodents as transmitters of zoonotic infections, local perceptions frame them as inevitable cohabitants, embedded within broader multispecies entanglements. The accelerating pace of environmental change which is marked by frequent flooding, expanding agricultural frontiers and conservation policies has intensified rodent proliferation and encounters, particularly in temporary farm settlements where structural precarity heightens human-rodent contact. At the same time, conservation initiatives that emphasise the protection of charismatic wildlife species inadvertently create complex ecological interactions, allowing rodents to flourish. By interrogating these intersections of environmental dynamism, governance and livelihood practices, this article argues that human-rodent entanglements in Kilombero problematise dominant One Health narratives of zoonotic risk by emphasising cohabitation and by tracing rodent lives beyond farms and biosecurity underpinnings. This article, therefore, calls us to rethink zoonoses through the lens of multispecies interactions, lay knowledges and environmental complexities.