Illicit drug use disparities persist across racial and ethnic and sexual identity groups. This study examined associations between sexual identity, race/ethnicity, and drug use patterns, focusing on types and usage within the past year. Using data from the 2021-2023 National Survey on Drug Use and Health (n = 129,823), multinomial logistic regression was used to assess drug use patterns. Key predictors included sexual identity (heterosexual, lesbian/gay, and bisexual) and race/ethnicity (White, Black, Asian, Hispanic, and Others), controlling for socioeconomic factors. Bisexual individuals had the highest drug use rates among sexual minority groups, particularly for polysubstance use (14.29%). White individuals reported the highest overall prevalence (72.55%), while Black and Asian individuals had lower rates. Drug use was highest among young adults (32.01%) and declined with age. Among racial groups, Black individuals exhibited the highest drug misuse risk (interaction model: single-drug use RRR = 2.70, 95% CI = [2.38, 3.05]; polysubstance use RRR = 1.70, 95% CI = [1.48, 1.95]), followed by Asian individuals (single-drug use RRR = 2.21, 95% CI = [1.72, 2.85]; polysubstance use RRR = 1.78, 95% CI = [1.38, 2.30]). Among sexual identity groups, Black bisexual individuals were the most vulnerable (RRR = 1.50, 95% CI = [1.03, 2.19]), highlighting the compounded risks faced by individuals at the intersection of racial and sexual minority identities. Findings emphasize the need for culturally responsive interventions targeting bisexual individuals and racial/ethnic minorities to reduce disparities and improve public health outcomes.