Tuberculosis remains a major health problem due to drug resistance and co-infection. Discovery of new drugs to counter tuberculosis is an urgent need. Multi-targeting strategy is one among the effective approach to combat the disease. Multi-targeting has minimal adverse effects. It is also difficult for Mycobacterium tuberculosis to survive and evolve into more drug-resistance strains in case of multi targeting. Lipases Rv0183 and Rv3802c were chosen as drug targets for the current study which are involved in the pathogen’s lipid and cell wall metabolism respectively. Seven potential dual inhibitors of tetrahydropyranyl and dibenzofuranone derivatives were discovered targeting respective substrate binding pocket of Rv0183 and Rv3802c. Molecule ZINC43860875 is the best hit with predicted free energy of binding (ΔG) of -10.80 and -10.97 kcal/mol against Rv0183 and Rv3802c respectively. Based on contact footprinting studies, several molecules were designed with better ΔG through modification of functional groups that favor van der Waals and ionic interactions. Molecule Rv0183-1 (combination of potential inhibitors ZINC43860875, ZINC28262919 and ZINC11616855) was identified as potential dual inhibitor against Rv0183 and Rv3802c with ΔG of - 18.08 and -16.14 kcal/mol respectively. The current study paves way towards design and development of new multi-target inhibitors to combat tuberculosis.