BACKGROUND: Roadmap 1.0 is a mobile health app that was previously developed for caregivers of patients who have undergone hematopoietic stem cell transplantation (HSCT). Formative research targeted toward its end users (caregivers) can help inform app design and development, allowing additional components to be incorporated into the app, which can then be tested in a future randomized controlled trial. OBJECTIVE: This study aimed to create a methodologically rigorous national survey that would help inform the development of Roadmap 2.0. METHODS: We conducted a prospective, qualitative research study that took place between November 18, 2018, and February 7, 2019, in a blood and marrow transplant unit within a large academic medical institution in the midwestern part of the United States. Cognitive interviews, including think-aloud and verbal probing techniques, were conducted in 10 adult caregivers (≥18 years) of patients who had undergone HSCT. RESULTS: Most participants were female (9/10, 90%), white (9/10, 90%), married (9/10, 90%), employed at least part time (6/10, 60%), caregivers of adult patients (7/10, 70%), and had some college education (9/10, 90%) and an annual household income of $60,000 or higher (6/10, 60%). All but one interview was audio-recorded, with permission. Overall, participants were engaged in the cognitive interview process of the draft survey, which included 7 topics. The interviews highlighted areas wherein survey items could be further refined, such as offering more response choices (eg, "NA") or clarifying the type of transplant (eg, autologous or allogeneic) or context of transplant care (eg, pre-HSCT, during HSCT, post-HSCT, inpatient, and outpatient). Apart from these findings, the items in demographics, caregiving experiences, technology, positive activities, and mood were generally interpreted as intended. On the basis of the transcript data and field notes by the interviewer, items within self-efficacy (Caregiver Self-Efficacy Scale) and coping (Brief Coping Orientation to Problems Experienced inventory) questionnaires generated more confusion among interviewer and participants, reflecting difficulties in interpreting the meaning of some survey items. CONCLUSIONS: This study incorporated the four cognitive aspects of survey methodology that describe the question-answering process-(1) comprehension, (2) information retrieval, (3) judgment and decision making, and (4) responding-by using the think-aloud and probing techniques in cognitive interviews. We conclude that this methodologically rigorous process informed revisions and improved our final questionnaire design. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.49188.