To determine appropriate treatment doses of cold atmospheric plasma (CAP), the Canady Helios Cold Plasma Scalpel was tested across numerous cancer cell types including renal adenocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma, ovarian adenocarcinoma, and esophageal adenocarcinoma. Various CAP doses were tested consisting of both high (3 L/min) and low (1 L/min) helium flow rates, several power settings, and a range of treatment times up to 5 min. The impact of cold plasma on the reduction of viability was consistently dose-dependent; however, the anti-cancer capability varied significantly between cell lines. While the lowest effective dose varied from cell line to cell line, in each case an 80–99% reduction in viability was achievable 48 h after CAP treatment. Therefore, it is critical to select the appropriate CAP dose necessary for treating a specific cancer cell type.