The fourth wave of the opioid crisis is characterized by increased use and co-use of methamphetamine. How opioid and methamphetamine co-use is associated with health care use, housing instability, social service use, and criminal justice involvement has not been studied and could inform future interventions and partnerships. To estimate service involvement across sectors among people who reported past year opioid and methamphetamine co-use, methamphetamine use, opioid use, or neither opioid nor methamphetamine use. We examined 2015-2018 data from the National Survey on Drug Use and Health. We used multivariable negative binomial and logistic regression models and predictive margins, adjusted for sociodemographic and clinical characteristics. Nonelderly US adults aged 18 or older. Hospital days, emergency department visits, housing instability, social service use, and criminal justice involvement in the past year. In adjusted analyses, adults who reported opioid and methamphetamine co-use had 99% more overnight hospital days, 46% more emergency department visits, 2.1 times more housing instability, 1.4 times more social service use, and 3.3 times more criminal justice involvement compared with people with opioid use only. People who used any methamphetamine, with opioids or alone, were significantly more likely be involved with services in 2 or more sectors compared with those who used opioids only (opioids only: 11.6%; methamphetamine only: 19.8%; opioids and methamphetamine: 27.6%). Multisector service involvement is highest among those who use both opioids and methamphetamine, suggesting that partnerships between health care, housing, social service, and criminal justice agencies are needed to develop, test, and implement interventions to reduce methamphetamine-related morbidity.