Prevention　of　Clostridium　difficile　infection　is　challenging　worldwide　owing　to　its　high　morbidity　and　mortality　rates.　C.　difficile　is　currently　being　classified　as　an　urgent　threat　by　the　CDC.　Devising　a　new　therapeutic　strategy　become　indispensable　against　C.　difficile　infection　due　to　its　high　rates　of　reinfection　and　increasing　antimicrobial　resistance.　The　current　study　is　based　on　core　proteome　data　of　C.　difficile　to　identify　promising　vaccine　and　drug　candidates.　Immunoinformatics　and　vaccinomics　approaches　were　employed　to　construct　multi-epitope-based　chimeric　vaccine　constructs　from　top-ranked　T-　and　B-cell　epitopes.　The　efficacy　of　the　designed　vaccine　was　assessed　by　immunological　analysis,　immune　receptor　binding　potential　and　immune　simulation　analyses.　Additionally,　subtractive　proteomics　and　druggability　analyses　prioritized　several　promising　and　alternative　drug　targets　against　C.　difficile.　These　include　FMN-dependent　nitroreductase　which　was　prioritized　for　pharmacophore-based　virtual　screening　of　druggable　molecule　databases　to　predict　potent　inhibitors.　A　MolPort-001-785-965　druggable　molecule　was　found　to　exhibit　significant　binding　affinity　with　the　conserved　residues　of　FMN-dependent　nitroreductase.　The　experimental　validation　of　the　therapeutic　targets　prioritized　in　the　current　study　may　worthy　to　identify　new　strategies　to　combat　the　drug-resistant　C.　difficile　infection.