A quantitative method to assess the in vitro foreign body reaction (FBR) of mononuclear phagocytes (MP) to polymers relevant in implants for prosthetics, advanced therapies, and regenerative medicine is presented. It integrates single‐cell force spectroscopy (SCFS) with immunogenic profiles of the MPs. In cell force spectroscopy experiments a single phagocyte, linked at the end of an atomic force microscopy cantilever, probes the adhesion forces between the cell and the polymer surface. SCFS measures adhesion forces in a range from 10 pN to 100 nN and with spatial resolution from cell size down to nanometers, accessing the early adhesion events established at contact times between milliseconds and minutes. The time evolution within the first 60 s of the adhesion force between the phagocyte and the polymer surface before and after the treatment with an immunosuppressive drug, viz. Minocycline, a Federal Drug Administration (FDA)‐approved third generation tetracycline with anti‐inflammatory effects, is then studied. The adhesion force values measured at the single cell level is shown to correlate to the immunogenic profiles obtained by analysis of biomarkers and morphology of the MPs in culture. Also, Minocycline causes a decrease of both proinflammatory gene expression profiles and adhesive forces of single cells