Infections of the skin and soft tissues caused by Vancomycin-nonsusceptible Coagulase-negative Staphylococci (VNS-CoNS) are becoming increasingly problematic as they spread throughout urban and rural communities. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI ToF MS) was used to determine the species of the isolated VNS-CoNS and the pattern of resistance to many antibiotics it displayed. From a total of 256 clinical samples, comprising pus, abscess, ear swabs, eye swabs, and aspirates, 91 CoNS isolates were biotyped and subsequently characterized with MALDI-TOF MS. Biofilm assays, Vancomycin susceptibility testing, and gene signature analysis of Staphylococci was also conducted. In comparison to the lower biotyping detection rate (P=0.001), MALDI-TOF had a 99.4% (CI 95, 0.775-0.997, positive predictive values, 90.2%) detection rate for 91 CoNS isolates of S.cohnii (2.3%), S.condimentii (3.4%), S. saprophyticus (6.7%), and S.scuri (21.1%). Wound, ear, and aspirate samples from 0.83 MARI or higher that lacked nuc, pvl, and spa genes aggregated into a distinct phylo-diverse group and were found primarily in urban and peri-urban areas. With a true-positive prediction AUC-ROC of 0.963, MALDI TOF-MS demonstrated excellent discriminatory power. All age groups showed resistance to VNS-CoNS, with the 25th and 75th percentiles showing the most resistance at MIC, more than equal to 16 µg/mL. Cutoff values for vancomycin greater than 8 µg/mL were seen in more than 10.5% of CoNS (P<0.05). Antibiotic resistant CoNS should be considered significant pathogens rather than contaminants. Urgent surveillance is needed in peri-urban and rural areas for biofilm-producing VNS-S. sciuri and S. condimentii strains due to the significant pathological tropism of these bacteria for skin infections, soft tissues, and wounds.