Non-thermal atmospheric pressure plasma sources operated in ambient environments are known to generate a variety of reactive oxygen and nitrogen species which could be applied for various biomedical applications. Herein, we fabricate a micro-dielectric barrier discharge plasma device by using screen-printing technology and apply it for studying immuno-stimulatory effects. We demonstrate a tumor-suppressive role for plasma-stimulated macrophages in metastatic solid cancers that directly elicit proliferation and are responsible for tumor relapse mediated by mesenchymal shift. Using microarray analysis, we observed that cold plasma stimulates and differentiates monocyte cells into macrophages as demonstrated by expression of several cytokine/chemokine markers. Moreover, plasma treatment stimulates the differentiation of pro-inflammatory (M1) macrophages to a greater extent. These stimulated macrophages favor anti-tumorigenic immune responses against metastasis acquisition and cancer stem cell maintenance in solid cancers in vitro. Differentiation of monocytes into anticancer macrophages could improve the efficacy of plasma treatment, especially in modifying pro-tumor inflammatory microenvironment through effecting highly resistant immunosuppressive tumor cells associated with tumor relapse.