RNA virus infections have been a leading cause of pandemics. Aided by global warming and increased connectivity, their threat is likely to increase over time. The flaviviruses are one such RNA virus family, and its prototypes such as the Japanese encephalitis virus (JEV), Dengue virus, Zika virus, West Nile virus, etc., pose a significant health burden on several endemic countries. All viruses start off their life cycle with an infected cell, wherein a series of events are set in motion as the virus and host battle for autonomy. With their remarkable capacity to hijack cellular systems and, subvert/escape defence pathways, viruses are able to establish infection and disseminate in the body, causing disease. Using this strategy, JEV replicates and spreads through several cell types such as epithelial cells, fibroblasts, monocytes and macrophages, and ultimately breaches the blood-brain barrier to infect neurons and microglia. The neurotropic nature of JEV, its high burden on the paediatric population, and its lack of any specific antivirals/treatment strategies emphasise the need for biomedical research-driven solutions. Here, we highlight the latest research developments on Japanese encephalitis virus-infected cells and discuss how these can aid in the development of future therapies.