Due to the high effectiveness of cancer screening and therapies, the diagnosis of second primary cancers (SPCs) has increased in women with endometrial cancer (EC). However, there’s no previous literature mentioned about adequate evidence to support screening for SPCs in endometrial cancer. This study was aimed to develop effective risk prediction models of second primary endometrial cancer in women with obesity (Body-mass index; BMI > 25) and this study includes datasets of the incidence of SPCs and the other risks of SPCs in 4480 primary cancer survivors by a hospital-based cancer registry database. In our study, we found the obesity played a key role in SPCs. There’re 10 independent variables used as predicting variables, which corelated to obesity should be monitored for the early detection of SPCs in endometrial cancer. In conclusion, it is a promising SPCs prediction. The proposed scheme can support the important influence of obesity and clinical data representations in all cases after primary treatments. Our results suggested that obesity is still a crucial risk factor to SPCs in endometrial cancer.