Background <p>Real-time electronic patient-reported outcome (ePRO) symptom monitoring is a complex intervention with few examples of successful implementation at scale. A key challenge is designing a clear ePRO symptom monitoring workflow to support implementation into practice. We aimed to create an empirical and theory-informed site-specific workflow guided by the Action, Actor, Context, Target, Time (AACTT) implementation science framework.</p> Methods <p>A five-step process was undertaken to customize a generic ePRO symptom monitoring workflow to create a site-specific version: (1) design a generic ePRO symptom monitoring workflow through a qualitative study with key stakeholders; (2) conduct co-design workshops to understand stakeholder preferences regarding a site-specific version; (3) code co-design workshop data using the AACTT framework to produce a provisional site-specific version; (4) conduct a final co-design workshop using the AACTT framework to finalize stakeholder preferences for a site-specific version; and (5) code co-design workshop data using the AACTT framework to produce a final site-specific version.</p> Results <p>Participants (n = 27) included nine patients, four caregivers, four oncologists, four nurses, two pharmacists, two clinic administrators, and two Electronic Medical Record (EMR) analysts. Provisional and final site-specific workflows were generated outlining the key AACTT components for each step of ePRO symptom monitoring.</p> Conclusion <p>We demonstrated the value in using the AACTT to guide the co-design of a site-specific workflow for ePRO symptom monitoring. By describing this process in detail, we will enable others to replicate this process for creating site-specific workflows not only for ePRO symptom monitoring, but for any complex clinical process.</p>