ObjectiveTo examine the associations of body mass index (BMI) and chemotherapy emetogenic risk with sleep disturbance in patients with cancer and to explore their multiplicative interaction and joint associations.MethodsThis retrospective cross-sectional study analyzed the medical records of 300 patients with cancer who received chemotherapy at Wuhu Second People’s Hospital between January 2023 and February 2025. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Multivariable binary logistic regression models were used to examine the associations of BMI and chemotherapy emetogenic risk with sleep disturbance after adjustment for age, sex, cancer type, educational level, and marital status. Multiplicative interaction and joint-association analyses were conducted as exploratory analyses, using patients with normal weight receiving low-to-moderately emetogenic chemotherapy as the reference group in the joint-association analysis.ResultsA total of 153 patients (51.0%) had sleep disturbance. After adjustment for age, sex, cancer type, educational level, and marital status, underweight patients (aOR = 2.272, 95% CI: 1.180–4.374, P = 0.014), overweight/obese patients (aOR = 3.171, 95% CI: 1.707–5.893, P < 0.001), and patients receiving highly emetogenic chemotherapy (aOR = 3.009, 95% CI: 1.819–4.977, P < 0.001) had higher odds of sleep disturbance. The overall multiplicative interaction between BMI category and chemotherapy emetogenic risk was statistically significant (P for interaction = 0.008). In the joint-association analysis, underweight patients receiving highly emetogenic chemotherapy had higher odds of sleep disturbance (aOR = 7.373, 95% CI: 2.644–20.555, P < 0.001), while overweight/obese patients receiving highly emetogenic chemotherapy showed the highest observed odds (aOR = 13.794, 95% CI: 4.740–40.139, P < 0.001); 87.2% of patients in this subgroup had sleep disturbance.ConclusionsAbnormal BMI and high chemotherapy emetogenic risk were associated with higher odds of sleep disturbance among patients with cancer. The exploratory interaction and joint-association analyses suggested that patients with abnormal BMI receiving highly emetogenic chemotherapy, particularly those with overweight/obesity, may represent a clinically vulnerable subgroup requiring closer sleep assessment. Given the retrospective cross-sectional design, relatively small subgroup sizes, and wide confidence intervals, these findings should be interpreted as exploratory and do not establish causal relationships.