Nosocomial resistance in staphylococci and enterococci is challenging. The aim of this work was to conduct a multipoint study using molecular detections, antimicrobial resistances profiles, patient demographics and disease patterns for objective assessments of Staphilococcus aureus and other Gram-positive pathogens recovered from clinical infections in the Ha’il region. We have surveyed 188 non-duplicate Gram-positives against 22 antimicrobials for molecular-differentiation, resistance, patient demographics, and disease patterns from January–April 2021. According to definitions for acquired resistance, Staphylococcus aureus was the most frequent with multidrug resistant (65.4%), where MRSA was 60% (n = 72 out of 121). In age-identified patients, 43% were seniors ≥50 years, 38% 21–49 years, and 19% 0–20 years. In gender-identified patients, 63% were males, and 37% were females. While 25% of specimens were from the ICU, the majority (60%) of specimens were from surgical infection in other wards. Staphylococcus epidermidis was the second (15.4%) species of infection identified with 81% from bloodstream infections at the ICU and other wards. The majority of S. epidermidis patients (69%) were seniors ≥50 years, while other age groups 0–20 and 21–49 each had 14% isolates. Although S. epidermidis was multidrug-resistant, it was susceptible to many drugs. Enterococcus faecalis (13%) ranked third with two major infections; bloodstream (64%) and urinary-tract infections (36%) in mainly seniors (86%). Its isolates were fully resistant to oxacillin, penicillin, cefoxitin, and cefotaxime but nearly 100% susceptible to seven others. Other Gram-positive bacteria (6%) were susceptible to many antibiotics. The use of combinations of objective criteria is a well thought out approach in infection control. While the low-frequency of Gram-positives is an impressive achievement, future large-scale investigations should include all private hospitals, clinics and other cities over a longer sampling time to gain more insights. Although geriatric susceptibility can be justified by age and comorbidities, the staphylococcal infections in young adults and children is a global concern and warrants more vertical studies.