Bone metastases are a common and devastating complication of advanced-stage prostate cancer, yet effective therapeutic options remain limited. A major obstacle to progress is the lack of relevant ex vivo models that can maintain patient-derived bone metastatic tissue for detailed analysis. Bone scaffolds, offer great promise as platforms to recreate the complex bone structure and extracellular matrix (ECM) needed to support the growth of bone metastases. This project aimed to address this gap by optimising a decellularised bovine-derived bone scaffold for the long-term culture of bone metastatic prostate cells and evaluation of immune modulators. Using high-resolution CT imaging, scaffold selection was standardised based on bone density to account for architectural variability. Culture of RM-1-452F bone metastatic prostate cells on the bone scaffold, retained the loss of key immune-related markers, such as Interferon regulatory factor 7 (Irf7), a master regulator of type I interferon (IFN-I) cytokine signalling, and Major Histocompatibility complex I (MHC-1), assessed through RT-qPCR and flow cytometry. Interestingly, when cultured on the bone scaffold the parental RM-I-536 cell line, which has an intact IFN-I pathway, showed loss of Irf7 and Irf9 expression, consistent with metastatic bone lesions, suggesting that tumour-bone interactions may drive immune evasion and metastatic progression. Multiphoton microscopy further demonstrated successful tumour cell- engraftment throughout the scaffold, cell viability and responsiveness to IFN-I and IFN- II cytokines, as indicated by enhanced MHC-I and Programmed Death Ligand I (PD-L1) cell surface expression. Collectively, this work has led to the establishment of a robust, scalable platform for studying tumour-bone interactions and screening targeted therapies. This model has the potential to accelerate biologically guided therapeutic discovery and advance precision oncology for patients with bone metastases.