To outline the potential reasons for the persistent underutilization of rehabilitation services in the care of patients with advanced cancer, a literature review and post hoc analysis of data collected from 163 patients with stage IV breast cancer are used to examine the role of accumulated physical impairments and adverse symptoms in cancer-related disablement. Univariate and multivariate regression analyses were used to estimate the variance in functional outcomes (as measured by the Physical Function-10, Functional Independence Measure, and the Older Americans Resource Study subscales) explained by the presence and interaction of physical impairments, pain (Brief Pain Inventory scores), and exertional limitations (6-min walk test performance). A majority of patients had more than three impairments. Potentially catastrophic impairments, for example, paraparesis and hemiparesis, occurred in only 15% of patients. Although most specific impairments explained less than 5% of the variance in functional outcomes, a participant's total number of impairments was strongly correlated with his/her performance status and explained between 36% and 52% of the variance in functional outcomes. Brief Pain Inventory scores and exertional intolerance explained a greater proportion of the variance in functional outcomes than did the presence of impairments. Multivariate models using total number of impairments, Brief Pain Inventory scores, exertional intolerance, and their interactions accounted for up to 65% of the variance in functional outcomes. The disablement process in metastatic breast cancer is driven by the accrual of multiple physical impairments, adverse symptoms, and their interactions rather than by discrete and functionally catastrophic impairments. Without systematic disability screening, the detection of functional decline may remain challenging.