<p><i>Citrobacter koseri</i> is a Gram-negative, multidrug-resistant bacterium linked to severe infections in immunocompromised individuals and neonates. It is especially linked to sepsis and meningitis, which often lead to CNS abscesses in newborns. Most infections happen randomly, but some are passed down from parent to child. There have also been reports of hospital-acquired outbreaks in neonatal care units. Even though diagnostic and treatment methods have improved, the death rate is still high. About one in three affected babies dies, and almost half of them suffer long-term neurological damage. As antibiotic resistance becomes more common, there is a growing need to look into new ways to treat diseases, such as vaccines and new drug targets. In order to address this issue, a thorough in-silico methodology integrating subtractive proteomics and reverse vaccinology was employed to pinpoint potential therapeutic targets from the core proteome. Five multi-epitope vaccine constructs were created using B- and T-cell epitopes from prioritized proteins, based on epitope prediction. Physicochemical and docking analysis identified constructs V1 and V5 as having strong binding affinities to Toll-like receptors TLR4 and TLR2, respectively. Furthermore, MD simulations validated the structural stability of docked complexes. In-silico immune simulations revealed that the constructs might induce robust immune responses. Additionally, potential drug target proteins were subjected to druggability analysis. This study presents a promising computational framework for combating <i>C. koseri</i>, though experimental and animal model validations are necessary to confirm the findings of this study.</p>