Background: The frequency of young men with aggressive prostate cancer (PC) at diagnosis is increasing. Clinical, environmental, and genetic drivers of this change have not been well characterized. Methods: This multi-institutional study evaluated two cohorts; Cohort 1 completed enrollment and is reported here. Eligible patients (pts) had early-onset (age ≤ 60 years) PC with metastasis (N+ or M+) at diagnosis, or within 5 years of curative intent local therapy. Data were collected to define clinical, environmental, and genetic profiles, including ctDNA and whole genome and transcriptome sequencing using Tempus xE. Standard descriptive statistics were used. Results: 46 pts were enrolled. Median age at diagnosis was 55 (range 41-60 years); 85% were White, 15% were Black; 4% served in the military and 4% reported biochemical exposure. 85% reported a family history of cancer, 46% had family history of PC. Median PSA at diagnosis was 19 (range 1-534 ng/mL), 56% had a Gleason score of 9-10, and 56% had de novo metastatic PC. 46% had prior local therapy. Genetic data is available for 40 pts. The most frequent clinically significant mutations (≥10% for somatic, ≥2.5% for germline) are summarized. 23 unique germline and over 1,000 unique somatic mutations were identified. Germline mutations associated with hereditary PC were found in 15%, all were associated with DNA damage repair (DDR). Somatic mutations in DDR genes were found in 10%. Co-mutations in TP53 and BRAF were seen in 30%. Interestingly, there were also incidental germline mutations identified that are associated with cardiac (MYBPC, MYH7) and vascular (MYH11, ACTA2) conditions, among others. Conclusions: In this cohort study we identified an unexpectedly high frequency of family histories that were positive for cancer (85%), and specifically PC (46%). However, rates of germline mutations associated with hereditary PC were similar to previous studies (15%), suggesting the possibility that other novel hereditary mutations driving increased PC risk may be present. Increased rates of somatic mutations in BRAF (35%) were also seen. The high frequency of BRAF mutations, particularly those that co-occur with TP53 mutations, may be driving more aggressive disease. We also found enrichment of mutations associated with non-cancer hereditary syndromes, including hypertrophic cardiomyopathy. These are not usually included in cancer-focused genetic studies, suggesting broader testing that includes potentially actionable incidental findings should be considered. More work is needed to define characteristics of this high-risk population and optimize management.