Context: There is a scarcity of early palliative care interventions to support family caregivers of persons with advanced cancer living in the rural Southern U.S. Objective: The objective of this study was to adapt the content, format, and delivery of a six session, palliative care, telehealth intervention with monthly follow-up for rural family caregivers to enhance their own self-care and caregiving skills. Methods: Qualitative formative evaluation consisting of one-on-one, semistructured interviews with rural-dwelling persons with metastatic cancer (n = 18), their primary family caregiver (n = 20), and lay patient navigators (n = 26) were conducted to elicit feedback on a family caregiver intervention outline based on published evidence-based interventions. Transcribed interviews were analyzed using a thematic analysis approach. Coinvestigators reviewed and refined preliminary themes. Results: Participants recommended that intervention topical content be flexible and has an adaptable format based on continuous needs assessment. Sessions should be 20 minutes long at minimum, and additional sessions should be offered if requested. Faith and spirituality is essential to address but should not be an overarching intervention theme. Content needs to be communicated in simple language. Intervention delivery via telephone is acceptable, but face-to-face contact is desired to establish relationships. Other Internet-based technologies (e.g., video-conferencing) could be helpful, but many rural dwellers may not be technology savvy or have Internet access. Most lay navigators believed they could lead the intervention with additional training, protocols for professional referral, and supervision by specialty-trained palliative care clinicians. Conclusions: A potentially scalable palliative care intervention is being adapted for family caregivers of rural-dwelling persons with advanced cancer and will undergo piloting in a small-scale randomized controlled trial.