Background Syndemics (i.e., multiple, co-occurring, and synergistic conditions) contribute to elevated substance use among sexual and gender minority (SGM) people relative to heterosexual, cisgender people. Research suggests that syndemic-informed and SGM-tailored treatments are effective in substance use treatment among SGM people. However, few studies have examined 1) the proportion of substance use treatment facilities offering syndemic-informed, SGM-tailored treatment programming; and 2) the availability and accessibility of syndemic-informed, SGM-tailored treatment programs across the U.S. Methods We used the 2020 National Survey of Substance Abuse Treatment Services (N-SSATS) dataset to perform a latent class analysis examining whether substance use treatment facilities’ tailored treatment programs cluster together to form distinct classes indicating whether facilities offer syndemic-informed and SGM-tailored programming. We then used multinomial logistic regression to examine associations between class membership and facility availability and accessibility. Results Analyses revealed four classes of substance use treatment facilities’ tailored programs. Facilities with syndemic-informed and SGM-tailored treatment programs compared to facilities with no tailored programs were more likely to be in the Northeast compared to the Midwest and South; to offer payment assistance versus not offer payment assistance; and to be private, for-profit facilities versus public or non-profit facilities. Conclusions This study’s findings identify the need for more facilities with syndemic-informed and SGM-tailored treatment, particularly in the Midwestern and Southern U.S. regions. Facilities offering syndemic-informed and SGM-tailored treatment might present accessibility barriers for low-income SGM people, as they were more likely to be private, for-profit facilities; however, they were more likely to offer payment assistance.