Background: Ethiopia faces a rising and disproportionate cancer burden, particularly among women, with breast, cervical, and colorectal cancers representing majority of cases. Limited healthcare infrastructure, fragmented data systems, and late-stage detection contribute to high mortality rates, especially in rural areas where access to oncology services is constrained. These systemic gaps highlight the urgent need for integrated, scalable, and data-driven solutions to improve early detection, care coordination, and health information management across all levels of the healthcare system. Objective: This study aims to design and propose an informatics-enhanced model that will integrate a customized OpenMRS electronic medical record platform with the mHealth application iBreastCheck to strengthen cancer screening, data interoperability, and referral pathways in Ethiopia. The model will be tailored to leverage existing community health structures specifically Health Extension Workers (HEWs) and designed to function in low-connectivity settings, with the goal of improving early cancer detection and standardizing oncology data capture. Methods: A multi-phase implementation approach will be employed, beginning with stakeholder interviews and training of HEWs on iBreastCheck for community-based breast cancer education and risk assessment. In parallel, OpenMRS will be customized and deployed with oncology-specific modules to support interoperability, using HL7 and XML standards for data exchange, and configured for offline functionality. The system design will emphasize open-source technologies, SQL-based data querying, and integration with national digital health infrastructure, supported by partnerships with the Ethiopian Ministry of Health, WHO, and NGOs. Results: The integrated OpenMRS and iBreastCheck model is projected to enhance cancer data completeness, improve screening participation through community health workers, and reduce diagnostic delays. By enabling standardized digital workflows and facilitating communication between community and clinical levels, the system will support more timely referrals and consistent protocol adherence. The use of offline-capable, interoperable tools will ensure functionality even in settings with limited internet connectivity, broadening accessibility across rural and underserved regions. Conclusion: The combination of OpenMRS and mHealth technologies offers a feasible and Scalable, model for improving cancer screening and care coordination in low-resource settings like Ethiopia. By aligning technology design with local infrastructure and human resource capacities, this approach addresses critical gaps in the oncology care continuum and provides a replicable framework for other low- and middle-income countries implementing digital health solutions for cancer control.