Background <p>Function is critically important to cancer survivors, who are at risk of losing independence and mobility. But relatively, little is known about how pain, a widely prevalent symptom, contributes to functional decline. Understanding this may lead to earlier intervention and improved clinical outcomes.</p> Methods <p>Four hundred eighty-eight participants across five cancer centers with rehabilitation clinics completed the PROMIS Cancer Function Brief 3D profile assessment and the numeric pain rating scale (NRS) during ambulatory clinic visits. Key clinical and demographic factors, including age, cancer diagnosis and status, cancer treatment history, age, and the presence of potentially function-limiting non-cancer factors, were recorded. Pearson correlation coefficients were calculated to determine the relationship between NRS scores and the PROMIS domains, and a multivariable analysis followed by a post-hoc least square mean analysis was conducted to explore relationships between clinical and demographic factors and reduced function and higher pain.</p> Results <p>Patient-reported pain was moderately correlated with patient-reported physical function (<i>r</i> = 0.38), fatigue (<i>r</i> = −0.44), and social participation (<i>r</i> = 0.44). The presence of a non-cancer musculoskeletal impairment (<i>p</i> &lt; 0.001) and of metastatic disease (<i>p</i> = 0.002) was significantly associated with higher pain levels. Age, the presence of active cancer (compared to no evidence of disease), the use of an assistive device for ambulation, the presence of chemotherapy-induced peripheral neuropathy, and the presence of a non-cancer psychiatric co-morbidity were not significantly associated.</p> Conclusions <p>Cancer survivors with higher levels of pain are more likely to report functional decline. Non-cancer musculoskeletal factors are strong contributors to this pain, as is the presence of metastatic disease.</p>