Background: A CLIA-certified organoid based drug sensitivity assay (a cancer organogram) has been developed for all solid tumors. An actionable report of organogram sensitivities to endocrine, chemotherapy and targeted agents, produced a drug sensitivity score as a tool to inform therapy decision making. Objectives: To evaluate the success rate of organoid derivation, the organogram drug responses across cancer types and to analyze the impact of the organogram report on therapeutic decision making. Methods: From 2016 to 2020, 628 cancer organograms were performed, with 513 tumor samples from 419 cancer patients. Within 48 hours of collection, fresh samples of tumor cells obtained from core biopsies, surgical excisions, or fluids were cultured, the majority as 3D organoids. Drug screens were performed with a library of up to 220 drugs, and dose-response was evaluated across a range of concentrations for each drug. Organogram sensitivity was ranked as response in five categories based on SPM Score: Exceptional (SPM15/14), Good (13/12), Moderate to Low (11/9), and None( < 9). 118 drugs on average were tested per screen (range: 68-152), so in a total of 628 organograms, more than 70,000 individual drug trials have been performed. The median turnaround time was 28 days (range: 19.5-51.5). Results: Of the 513 collected samples, 314 were fresh specimens: 96 core biopsies, 151 surgical specimens, and 67 fluids (pleural effusions or ascites), with an organoid derivation success rate of 58.3%, 78%, and 88%, respectively. Overall success rate in organoid derivation was 70.2%. Samples with poor viability and low tumor cell count (22%) were rejected. The primary cancer types tested were ovarian (n = 92, 17.9%), breast (n = 73, 14.2%), colorectal (n = 70, 13.6%), pancreatic (n = 51, 9.9%), cholangiocarcinoma (n = 42, 8.1%), and other solid tumors (n = 185, 36%). Median age of patients was 56 years old (range: 5-83), most of them heavily pretreated. 20.45% of drugs screened had exceptional and good responses (SPM score 15-12) (SD: 17.92%). We reviewed genomic data from 374 third-party genomic reports. The most frequent genomic alterations found were TP53 (n = 143, 38.2%), BRCA1 and BRCA2 (n = 47, 12.5%) CDKN2A (n = 42, 11.2%), FGFR1/2/3/4 (n = 41, 10.9%), and PIK3CA (n = 38, 10.1%). Post-test treatment information is available for a subset of 61 patients. The treating physician made an organogram-guided therapeutic decision in 32/44 patients with post test treatment drugs scored (72%). Conclusions: The cancer organogram test has a high rate of success in generating an actionable report that identifies therapies for patients with limited therapeutic options, including those with no known genomic biomarkers. The organogram guided selection of therapeutics for a significant subset of patients, nearly 4 times the rate reported with genomic testing alone.