To address the complex nature of cancer occurrence and outcomes, approaches have been developed to simultaneously assess the role of two or more etiologic agents within hierarchical levels including the: (i) macroenvironment level (e.g., health care policy, neighborhood, or family structure); (ii) individual level (e.g., behaviors, carcinogenic exposures, socioeconomic factors, and psychologic responses); and (iii) biologic level (e.g., cellular biomarkers and inherited susceptibility variants). Prior multilevel approaches tend to focus on social and environmental hypotheses, and are thus limited in their ability to integrate biologic factors into a multilevel framework. This limited integration may be related to the limited translation of research findings into the clinic. We propose a "Multi-level Biologic and Social Integrative Construct" (MBASIC) to integrate macroenvironment and individual factors with biology. The goal of this framework is to help researchers identify relationships among factors that may be involved in the multifactorial, complex nature of cancer etiology, to aid in appropriate study design, to guide the development of statistical or mechanistic models to study these relationships, and to position the results of these studies for improved intervention, translation, and implementation. MBASIC allows researchers from diverse fields to develop hypotheses of interest under a common conceptual framework, to guide transdisciplinary collaborations, and to optimize the value of multilevel studies for clinical and public health activities.