Crops and livestock play a synergistic role in global food production and farmer livelihoods. Increasingly, however, crops and livestock are produced in isolation, particularly in farms operating at the commercial scale. It has been suggested that re-integrating crop and livestock systems at the field and farm level could help reduce the pollution associated with modern agricultural production and increase yields. Despite this potential, there has been no systematic review to assess remaining knowledge gaps in both the social and ecological dimensions of integrated crop and livestock systems (ICLS), particularly within commercial agricultural systems. Based on a multi-disciplinary workshop of international experts and additional literature review, we assess the current knowledge and remaining uncertainties about large-scale, commercial ICLS and identify the source of remaining knowledge gaps to establish priorities for future research. We find that much is understood about nutrient flows, soil quality, crop performance, and animal weight gain in commercial ICLS, but there is little knowledge about its spatial extent, animal behavior or welfare in ICLS, or the tradeoffs between biodiversity, pest and disease control, greenhouse gas (GHG) mitigation, and drought and heat tolerance in ICLS. There is some evidence regarding the economic outcomes in commercial ICLS and supply chain and policy barriers to adoption, but little understanding of broader social outcomes or cultural factors influencing adoption. Many of these knowledge gaps arise from a basic lack of data at both the field and system scales, which undermines both statistical analysis and modeling efforts. Future priorities for the international community of researchers investigating the tradeoffs and scalability of ICLS include: methods standardization to better facilitate international collaborations and comparisons, continued social organization for better data utilization and collaboration, meta-analyses to answer key questions from existing data, the establishment of long term experiments and surveys in key regions, a portal for citizen science, and more engagement with ICLS farmers.