Objective: In the present study, an attempt has been made for subtractive proteomic analysis approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using computational tools. Methods: Paralogous, redundant and less than 100 amino acid protein sequences were removed by using CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative Metabolic pathways analysis was performed to find unique and common metabolic pathways. The non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for drug targets while Psortb and CELLO were used to predict subcellular localization. Results: There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp. enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways. These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins showed druggability and can be used as a therapeutic target. Conclusion: Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic druggable proteins which are essential for the pathogen survival and non-homologous to human proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat against salmonellosis.