Haemophilus influenzae, a gram-negative, facultative anaerobic coccobacillus, is a member of Pasteurellaceae family. It causes a variety of invasive and non-invasive bacterial infections known as H. influenzae infections. The rise in antibiotic resistance alarms for the identification of novel therapeutic targets for treating H. influenzae infections. The emerging trends in the field of Pharmacoinformatics have aided in the prediction of novel putative therapeutic targets. Subtractive Genomics is a simple yet powerful approach for the identification of novel therapeutic targets for a bacterial pathogen. The purpose of the current study is to identify novel putative therapeutic targets for the treatment of H. influenzae infections. In this study, the core proteome of 72 strains of H. influenzae was analysed, and 115 proteins were found to be unique and non-homologous to the human proteome. Further screening of these proteins led to identification of 25 proteins involved in the 29 unique metabolic pathways of bacteria. We have identified five novel putative therapeutic targets for H. influenzae bacteria that are unique, non-homologous to the human proteome, essential for the bacterial survival, and involved in the unique metabolic pathways of bacteria.