AIM: Heart failure is a leading cause of hospitalisation and often coexists with seven comorbid conditions on average. This study aimed to examine the gender differences in disease burden, symptom burden, and quality of life among older adults with heart failure and multimorbidity. DESIGN: Cross-sectional study. METHODS: This study utilised a baseline survey from an ongoing cohort study in 2022-2023. Adults aged ≥ 50 years with heart failure and more than one chronic condition were recruited from a university-affiliated hospital using an electronic patient portal. Disease burden was measured using a modified Disease Burden Impact Scale. The Edmonton Symptom Assessment Scale and EuroQoL-5D-5L assessed symptom burden and quality of life. Gender differences in baseline outcomes were examined using Pearson's Chi-square tests, Welch's t-tests, and multiple linear regressions. RESULTS: Among 353 participants who completed the baseline survey, the mean (±SD) age was 70 (±9.5) years, and 50.1% were women (mean age: 67 ± 9 vs. men: 72 ± 10). In adjusted models, women had 4.9 points higher disease burden (p = 0.003) and reported higher symptom scores of pain (p = 0.018), tiredness (p = 0.021), nausea (p = 0.007), and loss of appetite compared to men (p = 0.036). Women had significantly more moderate/severe problems in usual activities and pain/discomfort and 0.07 points lower EuroQoL index than men (p = 0.010). CONCLUSIONS: There were gender differences in disease/symptom burdens and quality of life. Women living with heart failure and multimorbidity had higher burdens but lower quality of life. IMPACT: Identifying gender differences among people with heart failure and multimorbidity can be the first step to explaining health disparities. Research should take more inclusive and equitable approaches to address these differences. Healthcare providers, including nurses, should implement targeted strategies for effective multimorbidity management by considering these differences and disparities in clinical settings. REPORTING METHOD: STROBE checklist, cross-sectional. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.