Real‐time monitoring of the cell/biomaterial interface for biomedical applications can significantly improve the assessment of biomaterials. However, currently there are no multiparametric real‐time monitoring systems for the ex vivo assessment of biomaterials. This study presents a method for monitoring of cell and tissue response to biomaterials based on microsensor read‐outs of pH, O2, and impedance. In vitro, the sensors are compatible with cells implants. For ex vivo measurements, either a biodegradable polymer poly(lactic‐co‐glycolic acid) or a protein‐repellent plasma polymer nanofilm is coated onto sensor arrays and placed on the chorioallantoic membrane of avian embryo ex ovo cultures. Signals related to dissolved oxygen, pH, and electrical impedance are continuously acquired for up to 90 h. Optical observation, immunohistochemical examination of CD45, and Haematoxylin and Eosin (H&E) staining show different unspecific immune responses. Tissue inflammation, capsule formation, and neovascularization are observed. These results correlate well with the type of coating material and the signal patterns acquired by the chemosensors. In addition, tissue death can be inferred from sensor signal patterns. This system is intended to enable continuous monitoring of biomaterials and is envisioned as a prescreening tool to provide real‐time monitoring of cell/biomaterial interface and also to reduce animal testing for biomaterial assessment purposes.