e24014 Background: Cardio-oncology traditionally focuses on cardiotoxicity prevention and acute cardiovascular-events. However, the functional, vocational, and mental health challenges that define daily survivorship remain largely hidden, representing a critical gap in holistic care. Methods: Utilizing the 2024 National Health Interview Survey (NHIS), we analyzed a nationally representative cohort of U.S. adults (≥18 years) across four groups: (1) Controls (no cancer or CVD), (2) CVD only, (3) cancer only, and (4) cardio-oncology. We evaluated five patient-centered metrics reflecting quality of life: functional and work limitations, assistive equipment use, personal assistance needs, and overall disability. Multivariable regression models, using Taylor series linearization for complex survey weighting, were adjusted for age, sex, race, hypertension, diabetes, hyperlipidemia, smoking, psychological distress (K6 score), and insurance status. Results: Among 32,599 adults (Weighted N = 259.7M), 2.9% lived with cardio-oncology multi-morbidity (weighted N = 5.34M; mean age 73y). After multivariable adjustment, functional limitations were highest in the cardio-oncology (63.6%, OR 2.34 [95%CI 1.89-2.88]), exceeding both CVD only (OR 1.99) and cancer only (OR = 1.26) groups. This population was also at the highest risk of disability (OR 2.74) and work limitations (31.7%, OR = 2.53). One in five cardio-oncology survivors reported severe mobility impairment (difficulty walking/steps), with a need for assistive equipment (OR = 2.86) and personal assistance (OR = 1.38). Conclusions: Cardio-oncology survivors face a functional and vocational burden significantly exceeding that of cancer or CVD alone. Care models must expand beyond event prevention to integrate routine functional screening and early rehabilitation to preserve quality of life in this high-risk population. Adjusted odds ratios by disease phenotype. Outcome CVD Only (vs. Control) Cancer Only (vs. Control) Cardio-Oncology (vs. Control) OR (95% CI) OR (95% CI) OR (95% CI) Functional limitation 1.99 (1.75–2.28) 1.26 (1.14–1.39) 2.34 (1.89–2.88) Uses special equipment 2.56 (2.20–2.98) 1.26 (1.08–1.46) 2.86 (2.32–3.53) Needs assistance 1.51 (1.17-1.94) 0.84 (0.64-1.12) 1.38 (0.99-1.92) Work limitation 2.12 (1.88-2.39) 1.19 (1.07-1.33) 2.53 (2.11-3.03) Disability 2.20 (1.90–2.56) 1.11 (0.96–1.29) 2.74 (2.26–3.32) Note: Models adjusted for age, sex, race, hypertension, diabetes, hyperlipidemia, smoking status, psychological distress, and insurance type. Reference group = Adults with no history of cancer or CVD. CVD = Cardiovascular disease; OR = Odds Ratio; CI = Confidence Interval.