BACKGROUND: Stroke has the highest disability-adjusted life-years lost in any disease, and approximately one-third of the patients get aphasia. Computers and tablets are innovative and aid in intensive treatments in speech rehabilitation for patients with aphasia. However, mechanical training limits the help to patients. OBJECTIVE: This study aims to provide a framework for an integrated virtual reality (VR) app to provide speech rehabilitation for patients with aphasia. METHODS: The content was generated through an in-depth literature review and discussion with experienced rehabilitation physicians and occupational therapists. We then conducted a 2-round Delphi study with 15 experts from hospitals and universities to rate the content using a 5-point Likert scale. The app was developed by an interdisciplinary team involving VR, medical science of rehabilitation, and therapeutic rehabilitation. Pilot usability testing of this novel app was conducted among 5 patients with aphasia, 5 healthy volunteers, 5 medical staff, and 2 VR experts. RESULTS: We designed 4 modules of speech rehabilitation: oral expression, auditory comprehension, cognition, and comprehensive application. Our VR-based interactive and intelligent app was developed to provide an alternative option for patients with aphasia. Pilot usability testing revealed user satisfaction with the app. CONCLUSIONS: This study designed and tested a novel VR-based app for speech rehabilitation specifically adapted to patients with aphasia. This will guide other studies to develop a similar program or intelligent system in a clinical setting.