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Background: Whereas the increased use of substances in sexual and gender minority (SGM) samples has been well documented, further person-centered analyses are necessary to better understand the unique profiles of SGM individuals and substance use. Methods : Utilizing a sample of 1,852 SGM emerging adults ( M age = 23.31) recruited via Prolific, a latent profile analysis was conducted to determine profiles of ecological systems using self-esteem, hope for the future, minority group connection, and a history of childhood adverse experiences. These profiles were then used to explore intergroup differences in the use of substances (alcohol, cannabis, prescription opioids, hallucinogens, heroin, tobacco, and amphetamines). Results : Four profiles were identified in this sample: (1) moderate with low self-esteem (47.8%), (2) connected with low adversity (30.9%), (3) moderate with high self-esteem (11.5%), and (4) disconnected with adversity (9.7%). Significant differences between profiles in the frequency of use were found in all substances except for cannabis and hallucinogens. Of note, participants in the connected with low adversity profile reported significantly more frequent alcohol use ( M =  3.30) compared to the disconnected with adversity ( M  = 2.89) and the moderate with low self-esteem ( M  = 2.96) profiles. Additionally, the disconnected with adversity profile reported significantly more frequent tobacco use ( M  = 1.99) compared to all other profiles. Conclusion : With a majority of the sample fitting profiles marked by mental health concerns, the present study indicates the need to identify and address risk and protective factors for SGM emerging adults' substance use and highlights differences within the larger SGM community. Implications for improving mental health are described.