A framework was developed to characterize the antimicrobial use/antimicrobial resistance complex in livestock systems in Indonesia, Vietnam, and Thailand. Farm profitability, disease prevention, and mortality rate reduction were identified as drivers toward antimicrobial use in livestock systems. It revealed that antimicrobial use was high in all sectors studied, and that routine preventative use was of particular importance to broiler production systems. Misleading feed labeling was identified as a hurdle to the collection of accurate antimicrobial use data, with farmers being unaware of the antimicrobials contained in some commercial feed. Economic analysis found that the cost of antimicrobials was low relative to other farm inputs, and that farm profitability was precariously balanced. High disease and poor prices were identified as potential drivers toward economic loss. The research indicates that antimicrobial use in small-scale poultry production systems improves feed conversion ratios and overall productivity. However, data were limited to quantify adequately these potential gains and their impacts on the food supply. During the study, all countries embraced and implemented policies on better management of antimicrobial use in livestock and surveillance of antimicrobial resistance. Future policies need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region.