Sequencing-based precision medicine has significantly impacted cancer care, yet many colorectal cancer patients lack actionable alterations or develop resistance to targeted therapies. A novel approach involving droplet emulsion is employed to rapidly create Micro-Organospheres (MOS) from patient tissues for functional precision oncology. Clinical studies on metastatic colorectal cancer patients using this MOS-based precision oncology pipeline yield timely predictions correlated with patient responses. MOS capture original stromal cells, allowing T cell penetration and serving as a clinical assay for testing immuno-oncology therapies. Additionally, a high-throughput MOS screening platform is introduced, facilitating “virtual clinical trials” to account for patient diversity in determining drug efficacy.