With rapid advancement in wearable biosensor technology, systems capable of real time, continuous and ambulatory monitoring of vital signs are increasingly emerging and their use can potentially help improve patient outcome. Monitoring continuous body temperature offers insights into its trend, allows early detection of fever and is critical in several diseases and clinical conditions including septicemia, infectious disease and others. There is a complex interaction between physiological and ambient parameters including heart rate, respiratory rate, muscle rigors and shivers, diaphoresis, local humidity, clothing, body, skin and ambient temperatures among others. This article presents feasibility analysis of a wireless biosensor patch device called as VitalPatch in capturing this physio-ambient-thermodynamic interaction to determine core body temperature, and details comparative performance assessments using oral thermometer and ingestible pill as reference devices. Based on a study on a cohort of 30 subjects with reference oral temperature, the proposed method showed a bias of 0.1 ± 0.37 °C, mean absolute error (MAE) of 0.29 ± 0.25 °C. Another cohort of 22 subjects with continuous core body temperature pill as reference showed a bias of 0.16 ± 0.38 °C and MAE of 0.42 ± 0.22 °C.Clinical Relevance- Non-invasive, continuous and real time body temperature monitoring can lead to earlier fever detection and provides remote patient monitoring that can result in improved patient and clinical outcome.