Aims: Early detection of minimal residual disease (MRD) after curative surgery for oral cavity squamous cell carcinoma (OCSCC) remains challenging, with conventional surveillance often identifying recurrence only after significant progression. Circulating tumour DNA (ctDNA) and salivary genomic markers offer a promising approach for early, precise detection. This study provides an update from our prospective cohort evaluating the feasibility and clinical utility of personalised ctDNA assays and salivary biomarkers to detect MRD and predict recurrence. Methodology: A prospective cohort of 60 surgically treated OCSCC patients was recruited at a tertiary centre. Tumour tissue, blood, and saliva were collected longitudinally at defined peri-operative time points. Whole-exome sequencing (WES) of tumour and germline DNA generated patient-specific mutation profiles, from which bespoke ctDNA panels (~100 variants) were designed. Plasma ctDNA and salivary samples were assessed for tumour-specific variants, with detection patterns compared against clinical, radiological, and histopathological outcomes. Results: Preliminary analysis shows ctDNA and salivary tumour-specific DNA have strong potential for MRD detection. In patients who recurred, ctDNA positivity was evident weeks to months before clinical or radiologic confirmation. Salivary assays demonstrated concordance with ctDNA in several cases, particularly for local recurrence. In patients without recurrence, ctDNA levels declined to undetectable or baseline levels post-treatment. Bespoke panels demonstrated high concordance with tumour genomic profiles and strong analytical performance. Conclusion: Early findings indicate that personalised ctDNA and salivary genomic assays are feasible and have the potential to enable earlier recurrence identification with individualised surveillance. Full cohort analysis is ongoing to determine predictive performance for eventual clinical integration.