Objective: To obtain a thorough understanding of the complexity and dynamics of the social determination of HIV infection among inhabitants of Cartagena, Colombia, as well as their views on necessary actions and priorities. Methods: In a five-year ethnography of HIV/AIDS in collaboration with 96 citizens of Cartagena, different methods and data collection techniques were used. Through 40 in-depth interviews and 30 life histories of inhabitants, the scenario of HIV vulnerability was summarized in a diagram. This diagram was evaluated and complemented through group discussions with key representatives of local governmental and nongovernmental organizations and with people who were interested in the epidemic or affected by it. Results: The diagram illustrates the dynamic and complex interrelationships among structural factors (i.e., social determinants) of HIV infection, such as machismo; lack of work, money, and social services; local dynamics of the performance of the state; and international dynamics of the sexual tourism industry. On the basis of the diagram, groups of key representatives proposed prioritizing structural actions such as reducing socioeconomic inequalities and providing access to health care and education. Conclusions: The social determinants displayed in the diagram relate to historic power forces that have shaped vulnerable scenarios in Cartagena. Collaboration between participants and researchers generates conceptual frameworks that make it possible to understand and manage the complexity of HIV's social determination. This way of understanding effectively connects local inequalities with international flows of power such as sexual tourism and makes evident the strengths and limitations of current approaches to HIV prevention.