BackgroundAddressing the modifiable health behaviors of cancer survivors is important in rural communities that are disproportionately impacted by cancer (eg, those in Central Appalachia). However, such efforts are limited, and existing interventions may not meet the needs of rural communities.ObjectiveThis study describes the development and proof-of-concept testing of weSurvive, a behavioral intervention for rural Appalachian cancer survivors.MethodsThe Obesity-Related Behavioral Intervention Trials (ORBIT) model, a systematic model for designing behavioral interventions, informed the study design. An advisory team (n=10) of community stakeholders and researchers engaged in a participatory process to identify desirable features for interventions targeting rural cancer survivors. The resulting multimodal, 13-week weSurvive intervention was delivered to 12 participants across the two cohorts. Intervention components included in-person group classes and group and individualized telehealth calls. Indicators reflecting five feasibility domains (acceptability, demand, practicality, implementation, and limited efficacy) were measured using concurrent mixed methods. Pre-post changes and effect sizes were assessed for limited efficacy data. Descriptive statistics and content analysis were used to summarize data for other domains.ResultsParticipants reported high program satisfaction (acceptability). Indicators of demand included enrollment of cancer survivors with various cancer types and attrition (1/12, 8%), recruitment (12/41, 30%), and attendance (median 62%) rates. Dietary (7/12, 59%) and physical activity (PA; 10/12, 83%) behaviors were the most frequently chosen behavioral targets. However, the findings indicate that participants did not fully engage in action planning activities, including setting specific goals. Implementation indicators showed 100% researcher fidelity to delivery and retention protocols, whereas practicality indicators highlighted participation barriers. Pre-post changes in limited efficacy outcomes regarding cancer-specific beliefs and knowledge and behavior-specific self-efficacy, intentions, and behaviors were in desired directions and demonstrated small and moderate effect sizes. Regarding dietary and PA behaviors, effect sizes for fruit and vegetable intake, snacks, dietary fat, and minutes of moderate-to-vigorous activity were small (Cohen d=0.00 to 0.32), whereas the effect sizes for change in PA were small to medium (Cohen d=0.22 to 0.45).ConclusionsweSurvive has the potential to be a feasible intervention for rural Appalachian cancer survivors. It will be refined and further tested based on the study findings, which also provide recommendations for other behavioral interventions targeting rural cancer survivors. Recommendations included adding additional recruitment and engagement strategies to increase demand and practicality as well as increasing accountability and motivation for participant involvement in self-monitoring activities through the use of technology (eg, text messaging). Furthermore, this study highlights the importance of using a systematic model (eg, the ORBIT framework) and small-scale proof-of-concept studies when adapting or developing behavioral interventions, as doing so identifies the intervention’s potential for feasibility and areas that need improvement before time- and resource-intensive efficacy trials. This could support a more efficient translation into practice.