Simple Summary: Patient-reported outcome (PRO) scores can help to reduce barriers between patient expectations and caregiver perspectives. The relationship between PRO scores and social determinants has not been studied widely. At a single large urban institution, all patients with a new cancer diagnosis who completed a survey over a two-year period were included. The PRO survey recorded perceived outcomes for depression, fatigue, pain interference and physical function. Over the two-year period, 1090 patients were included. Married patients had overall better PRO scores for each domain. Patients who had the ability to use the online portal also had overall better PRO scores. Male patients and minority patients had worse pain scores. PRO scores varied by cancer site and in association with specific social determinants. Future interventions can address patient support by utilizing these findings. Patient-reported outcome (PRO) scores have been utilized more frequently, but the relationship of PRO scores to determinants of health and social inequities has not been widely studied. Our goal was to determine the association of PRO scores with social determinants. All patients with a new cancer diagnosis who completed a PRO survey from 2020 to 2022 were included. The PRO survey recorded scores for depression, fatigue, pain interference and physical function. Higher depression, fatigue and pain scores indicated more distress. Higher physical condition scores indicated improved functionality. A total of 1090 patients were included. Married patients had significantly better individual PRO scores for each domain. Patients who were able to use the online portal to complete their survey also had better individual scores. Male patients and non-White patients had worse pain scores than female and White patients, respectively. Patients with prostate cancer had the best scores while patients with head and neck and lung cancer had the worst scores. PRO scores varied by cancer disease site and stage. Social support may act in combination with specific patient/tumor factors to influence PRO scores. These findings present opportunities to address patient support at institutional levels. [ABSTRACT FROM AUTHOR]