ABSTRACT Point‐of‐care testing (POCT) has become a cornerstone of modern nucleic acid diagnostics by enabling rapid, sensitive, and decentralized detection of pathogens and genetic biomarkers. In recent years, POCT technologies have evolved from amplification‐centered assays to intelligent and data‐integrated analytical systems. This review comprehensively examines the conceptual and technological evolution of smart point‐of‐care (POC) nucleic acid testing platforms for public health. It first summarizes template and signal amplification chemistries, including polymerase chain reaction, isothermal amplification, strand displacement, and clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein‐mediated (CRISPR–Cas‐mediated) catalytic cascades, which establish the molecular foundations of analytical sensitivity and specificity. The integration of amplification reactions with microfluidic architectures, nanomaterial design, and portable instrumentation has enabled automated, miniaturized, and user‐friendly diagnostic platforms suitable for field applications. In parallel, the combination of chemometrics and artificial intelligence facilitates automated signal interpretation, adaptive calibration, and predictive modeling, transforming POCT into a self‐optimizing and data‐driven diagnostic paradigm. Applications in infectious‐disease surveillance, outbreak response, and community‐level screening demonstrate the translational potential of these systems in strengthening global health preparedness. Key challenges include assay standardization, cost effectiveness, data interoperability, and ethical and regulatory considerations, which need to be addressed for successful clinical translation and sustainable implementation. The continuous convergence of nucleic acid amplification chemistry, system integration, and computational intelligence is shaping the next generation of accessible, intelligent, and predictive diagnostic infrastructures for public health.
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