Abstract: Healthcare innovation in Africa requires an integrated framework that aligns healthcare service delivery, business sustainability, and technological advancements to ensure long-term impact. This study explores the intersection of healthcare, business, and technology, proposing a structured model for sustainable health innovation in Africa. Drawing on existing conceptual frameworks, the research identifies key enablers and barriers to innovation adoption, including regulatory constraints, financial limitations, infrastructural gaps, and resistance to change. The study employs a mixed-methods research approach, incorporating literature review, expert interviews, case studies, and surveys to analyze trends in health entrepreneurship and digital health adoption. Findings suggest that successful healthcare innovation requires adaptive policies, financial sustainability through entrepreneurial models, investment in digital infrastructure, and workforce capacity-building initiatives. The proposed framework emphasizes strengthening primary healthcare systems, fostering business-driven healthcare models, and leveraging digital health solutions to expand access and efficiency. Implications highlight the necessity of multi-stakeholder collaboration, regulatory reforms, and market-driven solutions to address systemic barriers. The study concludes that while healthcare innovation has transformative potential, achieving sustainability requires a coordinated effort from policymakers, healthcare providers, investors, and technology developers. Future research should focus on refining this framework with region-specific case studies and exploring emerging technologies that can enhance healthcare accessibility and affordability in Africa.