Vancomycin, a unique glycopeptide anti-microbial, was employed as a last option for treating multidrug-safe Gram-positive bacterial diseases. Vancomycin resistance was first noted in France in 1986, about 30 years after it was first administered. This became a significant health problem, requiring the immediate use of elective treatment approaches. Semi-synthetic antibacterial combinations and updated versions of previously utilized antibiotics are two examples of novel particle types. Vancomycin compounds that are semi- synthetic and have better lipid-restricting, film-disturbing, and restricting propensities have shown promise against Gram-positive and Gram-negative microscopic organisms. In this regard, different forms of no hereditary protection against vancomycin and the creation of several efficient strategies to counteract innate resistance in Gram-negative microbes, and acquired resistance in Gram-positive microorganisms, have been discussed.