Despite the seriousness of the disease carried by ticks, little is known about the Bourbon virus. Only three US states have recorded human cases of Bourbon virus (BRBV) infection; in all cases, a tick bite was connected with the onset of the illness. The Bourbon virus (BRBV) belongs to the Orthomyxoviridae family and Thogotovirus genus, originating in the states of the US, i.e., Kansas, Oklahoma and Missouri. The growing rates of BRBV infections in various parts of the US highlight the necessity for a thorough analysis of the virus’s transmission mechanisms, vector types and reservoir hosts. Currently, there are no vaccines or efficient antiviral therapies to stop these infections. It is imperative to produce a vaccination that is both affordable and thermodynamically stable to reduce the likelihood of future pandemics. Various computational techniques and reverse vaccinology methodologies were employed to identify specific B- and T-cell epitopes. After thorough examination, the linker proteins connected the B- and T-cell epitopes, resulting in this painstakingly constructed vaccine candidate. Furthermore, 3D modeling directed the vaccine construct toward molecular docking to determine its binding affinity and interaction with TLR-4. Human beta-defensin was used as an adjuvant and linked to the N-terminus to boost immunogenicity. Furthermore, the C-IMMSIM simulation resulted in high immunogenic activities, with activation of high interferon, interleukins and immunoglobulin. The results of the in silico cloning process for E. coli indicated that the vaccine construct will try its utmost to express itself in the host, with a codon adaptation CAI value of 0.94. A net binding free energy of −677.7 kcal/mol obtained during docking showed that the vaccine has a high binding affinity for immunological receptors. Further validation was achieved via molecular dynamic simulations, inferring the confirmational changes during certain time intervals, but the vaccine remained intact to the binding site for a 100 ns interval. The thermostability determined using an RMSF score predicted certain changes in the mechanistic insights of the loop region with carbon alpha deviations, but no major changes were observed during the simulations. Thus, the results obtained highlight a major concern for researchers to further validate the vaccine’s efficacy using in vitro and in vivo approaches.