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Background: While patient‐reported outcome measures (PROMs) have benefit in cancer clinical trials, real‐world applications are lacking. This study describes the method of implementation of a cancer enterprise‐wide PROMs platform. Methods: After establishing a multispecialty stakeholder group within a large integrated health system, domain‐specific instruments were selected from the National Institutes of Health's Patient‐Reported Outcomes Measurement Information System (PROMIS) instruments (pain interference, fatigue, physical function, and depression) and were administered at varying frequencies throughout each patient's cancer journey. All cancer patients with an oncologic visit were eligible to complete the PROMs prior to the visit using a patient portal, or at the time of the visit using a tablet. PROMs were integrated into clinical workflow. Clinical partnerships were essential for successful implementation. Descriptive preliminary data were compared using multivariable logistic regression to determine the factors associated with method of PROMs completion. Results: From September 16, 2020 to July 23, 2021, 23 of 38 clinical units (60.5%) implemented PROMs over 2392 encounters and 1666 patients. Approximately one third of patients (n = 629, 37.8%) used the patient portal. Black patients (aOR 0.70; 95% CI: 0.51–0.97) and patients residing in zip codes with higher percentage of unemployment (aOR: 0.07, 95% CI: 0.01–0.41) were among the least likely to complete PROMs using the patient portal. Conclusions: Successful system‐wide implementation of PROMs among cancer patients requires engagement from multispecialty stakeholders and investment from clinical partners. Attention to the method of PROMs collection is required in order to reduce the potential for disparities, such as Black populations and those residing in areas with high levels of unemployment. [ABSTRACT FROM AUTHOR]