In this paper, we first studied the change in resting metabolic rate (RMR) of 4 women during their pregnancy period. We retrospectively analyzed published data, which lacked rigorous statistical analysis. We introduced new data that helps to define RMR baseline variabilities and further compare the RMR fluctuations in steady physiological conditions (no pregnancy, no weight/diet/exercise regime change) to assess “true” RMR changes that can guide healthy weight management in pregnancy and other conditions. For each subject, the change in the RMR values were computed as the difference between the values during the metabolic rate inspection period and the baseline values. This difference was compared against the difference values of a reference subject, using a two-sided paired t-test at the significance level of 5%. Our results indicated that some subjects exhibit a statistically significant increase, some exhibit a decrease while others show no significant statistical variation in RMR values during pregnancy. These are important findings that demystify the old idea that the RMR of a pregnant woman “always” increases since she is generating a new life; rather, individualized physiological processes can produce metabolic changes that cannot be generalized and need individual RMR measurements throughout pregnancy. The insights gained from this study were then applied to retrospectively analyze the RMR of 20 subjects during a 6-month pilot weight loss intervention with 89% efficiency in weight loss. Our analysis revealed that there was no significant decrease in metabolic activities at the end of the program. Although this contradicts the belief that weight loss is associated with a decrease in metabolic activities, our results can be explained by the fact that subjects adhered to a healthy nutritional diet and regular exercise during the pro- gram; thus, the effect of weight loss on decreasing the RMR was counter-balanced by the effect of healthier diet and exercise on increasing the RMR, which helped in maintaining a steady and healthy metabolic rate. Both studies, pregnancy and weight loss interventions indicated that changes in the metabolic rate of pregnant women and individuals undergoing weight loss interventions are unpredictable, therefore there is an urgent need to implement personalized practices of weight management by periodically measuring RMR and adjusting food caloric intakes based on the individual’s metabolic rate.