This notice of funding opportunity (NOFO) seeks to support research aimed at holistic understanding of inter-individual or between-person differences in human pain conditions, focusing on Whole Person Health and enhancing pain treatment and management strategies towards personalized pain medicine. The goal of this NOFO is to support studies that focus on the collection of clinical and/or preclinical data to enable evidence-based modeling and understanding of inter-individual differences and/or heterogeneity of pain occurring with use of pain therapy/management, or with conditions such as a second pain condition, a comorbid health condition, a comorbid mental health condition, or conditions of use / misuse of opioids, alcohol or other substances. Applicants are encouraged to develop and implement novel, multidisciplinary research approaches, and include investigators with complementary expertise to fulfill the project and program goals. Input from patients and caregivers on the goals of the project is highly encouraged. Rigorous data-driven and evidence-based research approaches supported under this NOFO are expected to provide better understanding of biological and/or biopsychosocial underpinnings of inter-individual differences, heterogeneity, and stratification of persons with lived pain experience, which would accelerate the development of evidence-based solutions toward precision pain medicine.