Expanding diagnostic access across underserved and rural healthcare regions remains a critical determinant of health equity, early disease detection, and system-wide resilience. Infrastructure-driven approaches offer a pragmatic pathway to closing persistent diagnostic gaps caused by geographic isolation, workforce shortages, fragmented referral networks, and underinvestment in health facilities. This paper examines how strategic development of physical, digital, and organizational infrastructure can enable scalable, sustainable diagnostic services in low-resource and rural settings. It synthesizes evidence from health systems strengthening, rural health planning, and diagnostic network design to identify core infrastructure enablers that improve access, quality, and continuity of care. Key infrastructure components include decentralized laboratory hubs, modular and prefabricated diagnostic facilities, reliable power and water systems, cold-chain and specimen transport logistics, and interoperable health information systems. When combined with digital connectivity, telepathology, and point-of-care diagnostics, these assets reduce turnaround times, minimize patient travel burdens, and support timely clinical decision-making. The paper further highlights the role of workforce-aligned infrastructure, emphasizing training-centered facility design, task-shifting support spaces, and remote supervision platforms that extend specialist expertise into rural contexts. From a policy and financing perspective, infrastructure-driven expansion requires coordinated investment models that align capital planning with service delivery objectives. Public–private partnerships, performance-based financing, and regional diagnostic networks are discussed as mechanisms to de-risk infrastructure investment while ensuring affordability and long-term operability. Governance frameworks that integrate maintenance planning, quality assurance, biosafety, and regulatory compliance are identified as essential to preventing infrastructure decay and service fragmentation. The papaer concludes that infrastructure is not merely a physical input but a systems-level enabler of equitable diagnostic access. By embedding diagnostics within resilient infrastructure ecosystems that integrate technology, logistics, workforce capacity, and governance, health systems can extend high-quality diagnostic services to underserved and rural populations. Such infrastructure-driven strategies are foundational to universal health coverage, pandemic preparedness, and the reduction of avoidable morbidity and mortality in marginalized regions. Importantly, infrastructure planning must be context-sensitive, data-informed, and community-engaged, ensuring that diagnostic expansion aligns with local disease burdens, cultural practices, referral pathways, and sustainability constraints while promoting trust, utilization, and long-term health system integration across diverse rural geographies globally and fragile health markets.