Background Neurological illnesses require thorough examinations and evidence-based care to minimize consequences and enhance life quality. AimTo analyze nurses' knowledge, practices, and attitudes toward neurological examinations and identify associated challenges. Methods A descriptive cross-sectional design was employed. A total of 205 nurses from Kafr El Sheikh General Hospital were included in the study. Data was collected using an electronic questionnaire composed of two tools. The first tool assessed nurses' knowledge, practice, and attitudes toward neurological examinations, while the second tool explored challenges faced during these assessments. The questionnaire was distributed online, and the responses were analyzed for various demographic and professional factors. Results Nurses exhibited moderate knowledge (mean score: 22.22, SD: 5.22), positive attitudes (mean score: 8.78, SD: 2.81), and moderate practices (mean score: 1.96, SD: 1.36) regarding neurological assessments. Significant correlations were observed between knowledge and attitudes (r = 0.284, p < 0.001), knowledge and practice (r = 0.143, p = 0.041), and attitudes and practice (r = 0.186, p = 0.008). Major challenges included a dependence on technology with a mean score of 28.47 and, secondly, time constraints, which had a mean score of 15.29. For the demographic data that reached statistical significance, the factors included younger nurses, where 53.7% fell between the range of 20-30 years of education, and where 31.7% had their degree as a Nursing Technician. Therefore, younger and better-educated nurses were performing better. Targeted education thus made a difference, as 55.1% of the nurses who had training in neurological assessments reported improved knowledge and practice. Conclusion These findings highlight the need for targeted interventions to address the challenges nurses face, suggesting that providing additional training, fostering a supportive ward culture, and empowering nurses in their roles could enhance their confidence and competence in conducting neurological assessments, ultimately improving patient care.