This study pathogenomic to gain genetic characterizations of the first pathogenic strains of Macrococcus caseolyticus, obtained from the donkey in Sudan. The in-silico analysis revealed that a total of (714 genes) were associated with carbohydrate metabolism (187 genes), amino acid and derivatives (138 genes), protein metabolism (163 genes), cofactors, vitamins, prosthetic groups, pigments (103 genes), membrane transport (26 genes), RNA metabolism (37 genes) and stress response (29 genes). In addition, (31 genes) identified in the strain were involved in virulence, disease, and defense. Multiple antibiotic resistances were revealed (13gens) including methicillin resistance (mecI, mecA, mecR1) penicillin binding (PonA, pbpA, pbpH, pbpF and pbpB), Multidrug resistance (mdtH_1, ykka, ykkc and mdtH_2), Tetracycline resistance (tetA, tet38), multidrug export (emrB), multidrug efflux pump (sdrM, sepA) and putative multidrug resistance (emrK). Also, stress responses were (yug1_1, yug1_2, ydaG, ysnF, ydaD and ysnF) and cold shocks were (cspA_1, cspA_2 and cspG). Furthermore, hemolysin (HyA), staphylococcal secretory antigen (ssaA2, ssaA) and (7) seven Murein hydrolase regulation and cell death were identified. The organism consists of Tetracycline resistance gene in the plasmid and Three CRISPRs dan_contig_1, dan_contig_14 and dan_contig_27. The probability of being a human pathogen is 0.253 (PathogenFinder algorithm). Strain DaniaSudan is the first pathogenic strain of Macrococcus caseolyticus isolated from animal.