High-risk substance use among California’s youth is a public health crisis, and most substance use disorders go untreated. Influenced by targeted marketing and often unable to access quality prevention, harm reduction, and treatment services, California’s youth are set up to fail and faced with a largely punitive approach to substance use which is not only ineffective but harmful. By adopting and investing in evidence-based prevention, harm reduction, and treatment services, California can realize better health outcomes for youth. It is up to the State to address the social determinants of health that are associated with high-risk substance use and improve access to quality, youth-focused, culturally congruent services for substance use disorder.