We conducted literature searches and analyses to describe the current state of multilevel intervention (MLI) research and to identify opportunities to advance cancer control and prevention. We found single-level studies that considered other contextually important levels, and multilevel health-care systems research and community-wide studies. This literature is characterized by limited reporting of theoretical, contextual, temporal, and implementation factors. Most MLIs focus on prevention and screening, rather than diagnosis, treatment, or survivorship. Opportunities relate to 1) dynamic, adaptive emergent interventions and research designs that evolve over time by attending to contextual factors and interactions across levels; 2) analyses that include simulation modeling, or multimethod approaches that integrate quantitative and qualitative methods; and 3) translation and intervention approaches that locally reinvent MLIs in different contexts. MLIs have great potential to reduce cancer burden by using theory and integrating quantitative, qualitative, participatory, and transdisciplinary methods that continually seek alignment across intervention levels, pay attention to context, and adapt over time.