Bilateral elective nodal irradiation (ENI) remains standard for treating most head and neck squamous cell carcinomas (HNSCC) but is associated with significant toxicity. Advances in lymphatic mapping, particularly with SPECT/CT-guided sentinel lymph node (SLN) identification, have enabled more personalized radiotherapy strategies. This systematic review evaluates the efficacy and quality-of-life impact of ENI strategies using SPECT/CT-guided SLN mapping. This systematic review, conducted according to PRISMA guidelines, included ten studies published between January 2014 and March 2024, including prospective, retrospective studies, randomized trials, and systematic reviews, examining oncologic outcomes and toxicity in patients undergoing SPECT/CT-guided SLN mapping or individualized ENI. Findings show that in well-lateralized, early stage carcinomas, SPECT/CT-guided ENI safely allows for unilateral treatment in up to 82% of patients, with a low contralateral regional failure rate. This approach significantly reduces radiation exposure to organs at risk and rates of xerostomia, dysphagia, and hypothyroidism, leading to improved quality of life. However, its applicability to advanced or midline tumors remains limited. SPECT/CT-guided SLN mapping and individualized ENI offer a promising, less toxic alternative for selected patients. Further prospective, multicenter, and randomized studies are needed to confirm these benefits and support broader clinical adoption.