There are no models for assessing the factors that determine moderate to poor performance status in patients with cancer after chemotherapy. This study investigated the influencing factors and identified the best model for predicting moderate–poor performance status. A convenience sampling method was used. Demographic and clinical data and evaluation results for fatigue, pain, quality of life and Eastern Cooperative Oncology Group status were collected three days after the end of chemotherapy. Decision tree, random forest and logistic regression models were constructed. Ninety-four subjects in the case group had moderate to poor performance status, and 365 subjects in the control group had no or mild activity disorders. The random forest model was the most accurate model. Physical function, total protein, general quality of life within one week before chemotherapy, hemoglobin, pain symptoms and globulin were the main factors. Total protein and hemoglobin levels reflect nutritional status, and globulin levels are an index of liver function. Therefore, physical function, nutritional status, general quality of life and pain symptoms within one week before chemotherapy and liver function can be used to predict moderate–poor performance status. Nurses should pay more attention to patients with poor physical function, poor nutritional status, lower quality of life and pain symptoms after chemotherapy.