Background <p>Digital transformation is increasingly reshaping healthcare delivery worldwide; however, the adoption of digital health systems in developing and resource-constrained economies remains constrained by infrastructural limitations, poor alignment with clinical workflows, inadequate user involvement, and resistance to organizational change. Many digital healthcare initiatives in these settings continue to experience implementation and sustainability challenges, partly due to the absence of context-specific and evidence-based transformation models. Consequently, this study aimed to develop a customized evidence-based digital transformation framework to support the sustainable adoption of digital healthcare systems within tertiary and university teaching hospitals in developing economies.</p> Methods <p>This study emerged from a prolonged mixed-methods doctoral research project conducted across three tertiary healthcare institutions in southeastern Nigeria: the University of Nigeria Teaching Hospital (UNTH), ESUT Teaching Hospital (ESUTTH), and the National Orthopaedic Hospital Enugu (NOHE). The research involved close to 600 stakeholders, including doctors, nurses, medical records officers, patients, and clinical consultants. Data were collected through structured questionnaires, qualitative interviews, participatory co-design interactions, observational methods, usability testing, and iterative system evaluations. The study adopted an agile human-centered software engineering and participatory development approach to guide the design, implementation, and evaluation of the proposed TUMERIC digital healthcare support system and the resulting transformation framework.</p> Results <p>The findings demonstrated generally positive institutional readiness toward digital transformation, with over 70% of participating healthcare professionals indicating support for future digital initiatives within their institutions. Usability evaluations of the implemented TUMERIC system also demonstrated high levels of user acceptance and perceived usability among clinicians and patients. Qualitative findings further highlighted the importance of aligning digital systems with existing clinical workflows, involving end users throughout the development lifecycle, and addressing infrastructural and organizational constraints during implementation. These findings informed the development of the proposed evidence-based digital transformation framework tailored to resource-constrained healthcare environments.</p> Conclusion <p>The study demonstrates that agile human-centered and participatory design approaches can support the development and adoption of context-appropriate digital healthcare systems in developing economies. The proposed framework provides an empirically informed model that may assist healthcare institutions and policymakers in planning and implementing more sustainable and user-aligned digital transformation initiatives within tertiary healthcare settings.</p>