Francisella tularensis is the causal agent of a sporadic zoonotic disease in humans called tularemia or "rabbit-fever". This gram-negative, facultative intracellular, pleomorphic coccobacillus was identified nearly 100 years ago, but the nature of its pathogenic interactions remained largely undefined until recent times . It is a highly virulent pathogenic organism that was given highest priority in the offensive biological weapons programs of the Soviet Union and Francisella tularensis Schu S4 is the causal agent of a sporadic zoonotic disease known as Tularemia, which has shown epidemic outbreaks recently in certain parts of the world. This pathogen is a potential agent of biowarfare or bioterrorism and is classified as a category A pathogen by the National Institute of Allergy and Infectious Diseases. In this virulent strain, 453 genes have been identified as essential genes, indispensable for growth and survival of the pathogen. The functions of 44 proteins encoded by those essential genes were found to be hypothetical and thus defined as essential hypothetical proteins (EHPs). The current study used a wide range of in silico tools and servers to annotate the physicochemical, structural, and functional properties of these EHPs. Of all the EHPs, 24 were functionally annotated with a high degree of confidence and validated by Receiver Operating Characteristic curve analysis. Non-homology assessment revealed 20 pathogen-specific EHPs, which were further analyzed for protein-protein interactions and predicted for secondary and tertiary structure. All the 3D structures were checked on multiple quality assessment servers, and the best models were visualized. The outcome of the study could aid in enhancing current understanding of bacterial pathogenesis with novel drug and vaccine investigations.