Wearable microneedle (MN) sensors for continuous interstitial fluid (ISF) monitoring are emerging as transformative tools for real-time biochemical profiling in healthcare. Unlike point-of-care (POC) devices that provide single-time-point results, continuous MN systems deliver time-resolved molecular data over extended periods, enabling detection of rapid physiological changes and supporting timely, personalized interventions. This review focuses exclusively on continuous MN systems designed for on-body, long-term operation, integrating engineering fundamentals, clinical application priorities, and translational strategies for MN-based electrochemical ISF sensing. We describe how MN architecture, materials, and fabrication methods are optimized for long-term in vivo performance and outline core sensing modalities with an emphasis on electrochemical approaches. Three clinical domains are highlighted: chronic disease management, early disease detection, and therapeutic drug monitoring, each imposing distinct technical and operational challenges. Cross-cutting requirements such as antifouling, secure skin adhesion, and closed-loop integration are critically examined. Regulatory readiness and clinical workflow integration are discussed to align MN technologies with established pathways. By linking technical progress to clinical translation, this review provides a practical roadmap to accelerate MN-based continuous monitoring from laboratory innovation to real-world adoption.