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The Singapore National Precision Medicine (NPM) program is a three-phase whole-of-nation effort designed to develop scalable, evidence-based solutions for precision health tailored to Asia's diverse populations. Here we present NPM phase II (2020-2025), highlighting how large-scale precision medicine initiatives can drive new research insights, enable healthcare innovations and create economic value. Key achievements include the PRECISE-SG100K population dataset, which reflects Singapore's unique multi-ancestry Asian population; the successful translation of research findings into mainstream national healthcare using familial hypercholesterolemia as a use case; and the establishment of strategic public-private partnerships with diverse industry sectors. We also outline phase III (2025-2031), which aims to establish whole-genome sequencing as a foundational element of a patient's lifelong healthcare record for 10% of the population. NPM provides a model for how smaller countries, despite limited populations and finite resources, can contribute meaningfully to global scientific movements while preserving strategic independence and addressing national health challenges.