Containing outbreaks that might lead to pandemics is a crucial public health operation that is strengthened by clinical research studies on the etiologies, epidemiology, clinical manifestations, and case management processes of infectious diseases. The INA-RESPOND Network maintains an extensive and experienced research presence across Indonesia that is capable of conducting research on ongoing infectious disease outbreaks and difficult cases of unidentified etiology. This 5-year protocol will leverage the unique capacity of the INA-RESPOND Network to rapidly study sudden disease outbreaks, difficult infectious disease cases of unidentified etiology, and samples collected during historical outbreaks and cases of unknown etiologies. The outcomes of this research will significantly improve our understanding of circulating diseases in Indonesia, particularly those that are most challenging to identify and of greatest outbreak concern.