Precision medicine for paediatric and adult cancers that incorpo-rates drug sensitivity profiling can identify effective therapies forindividual patients. However, obtaining adequate biopsy samplesfor high-throughput (HTP) screening remains challenging, withtumours needing to be expanded in culture or patient-derivedxenografts, this is time-consuming and often unsuccessful. Herein,we have developed paediatric patient-derived tumour models usingan engineered extracellular matrix (ECM) tissue mimic hydrogelsystem and HTP 3D bioprinting. Gene expression analysis from aneuroblastoma and sarcoma paediatric patient cohort identifiedkey components of the ECM in these tumour types. Engineeredhydrogels with ECM-mimic peptides were used to bioprint andcreate patient-specific tumouroids using patient-derived cells fromxenograft models, and the approach was further confirmed ondirect patient tumour samples. Bioprinted tumouroids from thePDX models recapitulated the genetic and phenotypic character-istics of the original tumours and retained tumourigenicity. HTPdrug screening of these models identified individualised drug sen-sitivities. Our approach offers a timely and clinically relevanttechnology platform for precision medicine in paediatric cancers,potentially transforming preclinical testing across multiple cancertypes.