Rich in reactive oxygen and nitrogen species, cold atmospheric plasma has been shown to effectively control events critical to cancer progression; selectively inducing apoptosis, reducing tumor volume and vasculature, and halting metastasis by taking advantage of, e.g., synergies between hydrogen peroxide and nitrites. This paper discusses the efficacy, safety and administration of cold atmospheric plasma treatment as a potential tool against cancers, with a focus on the mechanisms by which cold atmospheric plasma may affect critical transitional switches that govern tumorigenesis: the life/death control, tumor angiogenesis and epithelial–mesenchymal transition, and drug sensitivity spectrum. We introduce the possibility of modeling cell transitions between the normal and cancerous states using cold atmospheric plasma as a novel research avenue to enhance our understanding of plasma-aided control of oncogenesis.