Homologous recombination repair (HRR) is a highly regulated DNA damage repair pathway responsible for high-precision repair of double strand breaks (DSBs). Homologous recombination deficiency (HRD), commonly caused by biallelic inactivation of canonical HRR genes (e.g. BRCA1, BRCA2, PALB2 and RAD51C), results in exacerbated genomic instability and hypersensitivity to platinum-based chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi) in cancer cells. Although this therapeutic vulnerability has been widely exploited for clinical management of ovarian, breast, and prostate cancer, a lack of reliable biomarkers for accurate HRD detection remains a major challenge in the clinical setting. Through The Advanced Genomics Collaboration (TAGC), a partnership between Illumina and the University of Melbourne, our team at the University of Melbourne Centre for Cancer Research (UMCCR) has established a tumour/normal whole genome and transcriptome sequencing (WGTS)-based tumour profiling pipeline to inform personalised cancer care for patients registered through The Cancer of Low Survival and Unmet Need (COLUMN), the Victorian Comprehensive Cancer Centre PRECISION (VCCC PRECISION), the Stafford Fox Rare Cancer (SFRC) and the SUPER-NEXT programs. As part of this pipeline, comprehensive assessment of HRD status is achieved by combining detection of genetic alterations in HRR genes, genomic instability, mutational signatures, as well as utilisation of genome-wide scar-based HRD classifiers, CHORD and HRDetect. Using this pipeline, 55 of 720 (7.6%) solid tumour WGTS cases reported between Feb 2019-Aug 2023 were classified as HRD. This in-depth approach has allowed 1) identification of HRD tumours in the presence or absence of pathogenic mutations in canonical HRR genes, expanding therapeutic options; 2) interpretation of variants of unknown significance in canonical HRR genes; and 3) clarification of resistance mechanisms.