ABSTRACT As “obesogenic environments” grow increasingly prevalent, obesity has become a pressing global health challenge. It has been somewhat overlooked that individual responses to this obesogenic condition tend to be varied, and the mechanism behind this variability remains poorly understood. In the current study, we seek to summarize recent studies of human subjects and rodents that aim to identify the predictive factors of the heterogeneity of obesity. These factors include baseline fat mass (FM), fat‐free mass (FFM), muscle oxidative capacity, VO 2 max, androgen level, plasma leptin level, physical activity (PA), energy intake (EI), and genes such as SFRP5 , MEST , and BMP3 . Influenced by both genetic and environmental conditions, these factors provide a comprehensive framework for understanding the causes why individuals, even under the same obesogenic environment, exhibit differing weight gain responses. Our review synthesizes the existing literature to highlight these predictive factors, such as FM and FFM, as strong potential indicators of future weight gain and obesity risk. Integrating these factors into a unified framework not only enhances our understanding of obesity susceptibility but also provides a foundation for developing personalized obesity prevention and treatment strategies.