Structural interventions alter the social, economic, legal, political, and built environments that underlie processes affecting population health. We conducted a systematic review of evaluations of structural interventions for HIV prevention in low- and middle-income countries (LMICs) to better understand methodological and other challenges and identify effective evaluation strategies. We included 27 peer-reviewed articles on interventions related to economic empowerment, education, and substance abuse in LMICs. Twenty-one evaluations included clearly articulated theories of change (TOCs); 14 of these assessed the TOC by measuring intermediary variables in the causal pathway between the intervention and HIV outcomes. Although structural interventions address complex interactions, no evaluation included methods designed to evaluate complex systems. To strengthen evaluations of structural interventions, we recommend clearly articulating a TOC and measuring intermediate variables between the predictor and outcome. We additionally recommend adapting study designs and analytic methods outside traditional epidemiology to better capture complex results, influences external to the intervention, and unintended consequences