The PICO (Population/Problem, Intervention, Comparison, Outcome) framework is widely accepted for posing evidence-based practice questions. This framework offers prelicensure nursing students a structured process for synthesizing nursing knowledge with the best available evidence to make decisions for practice. However, students in an international outreach course may find that evidence-based practice is not available in-country; furthermore, it may not be congruent with a population’s culture. Faculty guidance helps students enrolled in international outreach courses to integrate cultural competence into the PICO structure. A case study illustrates how the framework was applied during an undergraduate nursing outreach course to Nicaragua.