Introduction: HIV/AIDS continues to pose a significant global public health challenge, including in the MENA region. Insufficient HIV/AIDS knowledge among nurses compromises care quality for PLWHA, leading to stigmatizing attitudes and inconsistent adherence to universal precautions. Method: This cross-sectional study examined nurses' knowledge, attitudes, and practices (KAP) towards PLWHA. Data were collected from 563 nurses across five major governmental hospitals in Oman through self-administered questionnaires using convenience sampling. Results: The study highlighted unsatisfactory HIV/AIDS knowledge among nurses (mean = 14.30 out of 28). Nurses' attitudes towards PLWHA were moderate, yet 71.4% expressed fear of contracting HIV, and 41.7% believed in isolating PLWHA. Weak but significant positive correlations were found between knowledge-practice (r = 0.284), knowledge-attitude (r = 0.254), and attitude-practice (r = 0.097). Furthermore, 80.3% had no prior HIV training, but 68.4% expressed willingness to attend training. Conclusion: This study emphasizes the need for HIV/AIDS training to improve nurses' knowledge, attitudes, and practices. Recommendations include tailored educational policies to enhance care for PLWHA and to address HIV-related stigma in the MENA region.