This study evaluates within-subject temporal differences between tumor and body temperatures using three cancer models: melanoma, breast cancer, and colon cancer, to monitor the effects of immunotherapy and chemotherapy on temperature differences. In the melanoma arm, TRP-2 immunotherapy led to increased tumor temperatures compared to the control group, with significant overall treatment separation observed at 58 h into the treatment protocol. For breast cancer, AC-Taxol chemotherapy resulted in a drop in body temperature for both treatment and control groups, with significant treatment group separation on tumor vs. body observed at 96 h. In colon cancer, anti-PD-1 immunotherapy showed an upward trend in tumor temperatures, with significant separation from the control group at 94 h. A series of statistical tests, including mixed-model repeated measures and non-parametric tests, revealed significant differences in temperature trends between treatment and control groups for all cancer types. Furthermore, examination of radial smoothing repeated measures models revealed how the clinical application of this technology could be applied. These results suggest that temperature-based monitoring may be an effective tool for assessing therapeutic responses in cancer treatments, highlighting the utility of thermal measurements in evaluating immunotherapy and chemotherapy efficacy.