Indigenous adults (18 years or older) including parents, staff, and volunteers of an urban Indigenous youth after-school program participated in individual interviews (n = 10) as part of a community-based participatory research (CBPR) Indigenous harm reduction study to identify alcohol and other drug (AOD) content to include in prevention programming for youth participants. Adult findings were organized using a risk environment framework to identify culturally relevant social, physical, policy, and economic AOD risk factors for youth. We report where adult findings intersect with previously described youth results to establish a list of core content (i.e., culturally relevant AOD prevention activities and discussion topics) to guide program implementation. Core content includes intergenerational Indigenous perspectives (i.e., youth, adult, and elder) to reflect Indigenous cultural lifeways and values of protecting future generations. Findings may be highly relevant to other Indigenous after-school groups or others who wish to develop harm reduction prevention programming for urban Indigenous youth in the Pacific Northwest or beyond.