The health of adolescents, perhaps more than in any other period of their life, is shaped by the social determinants of health (SDH). The constellation of SDH that disadvantages a specific group's health may also make members of that population unable or unwilling to engage in health research. To build a comprehensive body of knowledge about how SDH operate within a specific social context, researchers must design studies that take into account how various vulnerabilities and oppressions may affect people's experiences of being recruited, interviewed and retained in a study. In 2014, we initiated a prospective cohort study with Latino youth living in the agricultural area of Salinas, California. We began this study with the understanding that it was imperative to develop methodological strategies that actively addressed potential challenges in ways that were culturally responsive, community engaged and inclusive. In this article, we describe our approach to developing best practices in four key areas: 1) building community partnerships and engagement; 2) consideration of staffing and staff support; 3) engaging youth's perspectives; and 4) developing culturally appropriate research protocols. In our sample of 599 participants, nearly all youth identify as Latinx (94 per cent), half (49 per cent) have at least one parent employed as a farmworker, 60 per cent reside in crowded housing conditions, and 42 per cent have mothers who did not complete high school. Given these multiple vulnerabilities, we view a robust number of youth expressing interest in study participation, the willingness of their parents to permit their children to be enrolled, and the achievement of an ambitious sample target as evidence that our efforts to undertake best practices in community-engaged and inclusive research were well received.