Rapid significant weight fluctuations can indicate severe health conditions such as edema due to congestive heart failure or severe dehydration that could require prompt intervention. Daily body weighing does not accurately represent the patient’s body weight fluctuations occurring within a day. The patient’s lack of compliance with tracking their weight measurements is also a predominant issue. Using shoe insole sensors embedded into footwear could achieve accurate real-time monitoring systems for estimating continuous body weight changes. Here, the machine learning models’ predictive capabilities for continuous real-time weight estimation using the insole data are presented. The lack of availability of public datasets to feed these models is also addressed by introducing two novel datasets. The proposed framework is designed to adapt to the patient, considering several unique factors such as shoe type, posture, foot shape, and gait pattern. The proposed framework estimates the mean absolute percentage error of 0.61% and 0.74% and the MAE of 1.009 lbs. and 1.154 lbs. for the less controlled and more controlled experimental settings, respectively. This will help researchers utilize machine learning techniques for more accurate real-time continuous weight estimation using sensor data and enable more reliable aging-in-place monitoring and telehealth.