Youth substance abuse is widely recognized as a major public health issue in Thailand. This study explores family and community risk and protective factors relevant to alcohol and illegal drug misuse in 1,778 Thai teenagers. Strong family attachment and a family history of antisocial behaviors were strongly associated with nearly all forms of substance abuse, with adjusted odds ratios ranging from 5.05 to 8.45. Community disorganization was strongly associated with self-reported substance use, although involvement in prosocial activities acted as a protective factor. The findings suggest that interventions that promote family cohesion and encourage community involvement may have considerable benefits in reducing substance abuse in Thai adolescents.