Salmonella enterica is a Gram-negative facultative anaerobic bacteria. It belongs to the family of Enterobacteriaceae. Infections caused by Salmonella species are major threat to the human and animal health. After 1-3 days of ingestion of contaminated food, the patient develops diarrhea, fever, vomiting, and abdominal cramps. The situation is exacerbated if not treated promptly. Whole genome sequencing projects of clinically significant serovars of S. enterica have opened new perspectives of medical research. Using the genomic data, novel approaches are being employed throughout the world to find new protein targets for drug designing and screening. Targeting the essential metabolic pathways of the bacteria is the approach which we have focused in our study. The protein sequence and metabolic pathway data of the core proteome of S. enterica was analyzed in comparison to that of Homo sapiens. Various computational tools (BLASTp, CD-HIT, and Shell scripting) and datasets (NCBI, DEG, and KEGG) were extensively utilized to find non-homologous and essential enzymes of the pathogen. We discovered 73 enzymes belonging to metabolic pathways found only in the bacteria but not in H. sapiens, and proposed them as potential drug targets. Later, we selected an essential outer membrane protein complex (LptD/E) of S. enterica involved in lipopolysaccharide assembly, as a target in search of an inhibitor of the PPI complex. Druggable sites at the interface of PPI were identified by PocketQuery followed by virtual screening of the ZINC database of commercially available compounds using the ZINCPharmer tool. Energy minimization and scoring of short-listed compounds was performed using SMINA. A rational screening of >10,000 compounds resulted in 3 compounds depicting favorable polar interactions and optimal conformation for binding with the LptD protein. We propose that this interaction may lead to block the LptD interaction with LptE and lipid molecules and in result may block the LPS assembly.