Background: Minimal residual disease (MRD) refers to a small number of cancer cells that remain in the body after curative-intent treatment, causing relapse and metastasis. Current tumor biomarkers and imaging methods have limited sensitivity and specificity to monitor MRD for solid tumors. Circulating tumor DNA (ctDNA) in liquid biopsy has emerged as a promising biomarker to detect MRD but current ctDNA assays remain mostly inaccessible and unaffordable for developing countries. Methods: In this prospective multi-center study, 441 Vietnamese patients diagnosed with breast, colorectal, gastric, lung, liver and ovarian cancers, eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived genomic alterations including actionable mutations in 95 cancer-associated genes. Our bioinformatic algorithm then ranked top alterations unique for individual patient, which were then used to monitor ctDNA presence in serial plasma samples collected before surgery and at scheduled visits after surgery by multiplex PCR and ultra-deep sequencing. Results: The assay had limit of detection for somatic mutations down to at least 0.05% variant allele frequency in liquid biopsy.The sensitivity to detect ctDNA in the pre-operative plasma was 91%, 95%, 70%, 77%, 69% and 47% for colorectal, liver, lung, ovarian, high-risk breast cancer and gastric cancer respectively; the specificity was >99%. After 18-month follow-up, our interim analysis revealed a promising 89% detection rate of post-operative ctDNA in all patients that had metastasis and recurrence (31/35), with the lead time of 2.5-13 months ahead of clinical diagnosis. Conclusions: The K-Track assay is streamlined and affordable with dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies. The assay could lay foundation to empower precision cancer medicine in Vietnam and developing countries.