Findings from the Youth19 survey of New Zealand secondary school students show that greater investment in drug harm prevention is needed, particularly for under-served populations. Indicators related to e-cigarette, tobacco, alcohol or cannabis use were investigated in 7721 survey participants: 1) past month use; 2) heavy use; 3) worry about use; 4) desire to cut down or stop; and 5) reported difficulty accessing cessation help. Despite many adolescents, particularly tobacco users, being worried about their drug use and wanting to cut down, they often found it difficult to get appropriate help. Populations with the highest needs on many indicators were Māori, Pacific and LGBTQ+ youth, those aged <16 years and those living in small towns, rural areas and the most socioeconomically deprived communities.