Chronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard as it will generate large clinical datasets including a diverse set of harmonized measurements. The Theoretical Model Working Group (TMWG) was established to guide BACPAC research, and to organize new knowledge within a mechanistic framework. This article summarizes the initial works of the TMWG. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity. During Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to PRISMA guidelines to establish working definitions, associated data elements (ADEs), and overall strength-of-evidence (SOE) for identified RPFs. These were subsequently integrated with expert opinion during Stage 3. The majority (∼80%) of RPFs had little SOE confidence, while 7 factors had substantial confidence for either a positive association (pain-related anxiety, serum c-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association (serum interleukin 1-beta/interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing) with cLBP. This theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and utilize a systems approach to develop tools and algorithms that disentangle the dynamic interactions between cLBP factors.