The use of telemedicine and e-Health applications is increasingly relevant in healthcare, especially among nursing staff working in hospital settings.Understanding how these professionals interact with health informatics tools not only informs clinical practice but also supports the ongoing integration of digital health technologies within the National Health System.To explore the attitudes of nursing staff in Peloponnese hospitals towards telemedicine and health informatics applications in their workplace Methods.A quantitative study was conducted among 305 nurses working in hospital centers across the Peloponnese region. Participants voluntarily completed a standardized and validated questionnaire distributed electronically via URL link and QR code.The sample was predominantly female (84.59%), mostly aged between 35–44 years. Over half (53.12%) showed moderate to negative awareness of telemedicine, and 68.85% reported no prior use of e-Health programs. Limited knowledge of Electronic Health Records was noted in 34.41% of respondents. Nevertheless, 69.18% believed that e-Health programs could enhance their work performance. University graduates had greater familiarity with digital health tools than those from technological institutes (59.34% vs. 31.06%). A majority (211 out of 305) expressed willingness to adopt telemedicine systems at work, although 89.5% reported lack of institutional support for professional development in e-Health.The findings reveal a significant gap in awareness and use of telemedicine and e- Health applications among nursing staff in Peloponnese hospitals, despite the majority recognizing their potential to improve workplace performance. This indicates a need for targeted education and institutional support to enhance digital health literacy and foster telemedicine adoption. The disparity in familiarity between university graduates and technological institute graduates suggests that educational background influences readiness to engage with health informatics. Addressing these gaps through professional development programs could accelerate the integration of telehealth services, improve patient care, and reduce healthcare costs. The current lack of institutional support highlights a critical area for policy intervention and resource allocation.While past barriers to telehealth exist, hospitals have recently started adopting strategies for implementation. Telenursing programs hold promise to reduce healthcare costs and enhance service delivery. Local healthcare units increasingly utilize internal resources to develop telemedicine initiatives.