Purpose <p>Our study identifies sociodemographic, clinical, and behavioral factors associated with serious psychological distress (SPD) among US adult cancer survivors, highlighting actionable targets for mental health interventions in survivorship care.</p> Methods <p>We analyzed 2024 National Health Interview Survey data from adults aged ≥ 18&#xa0;years with a self-reported history of cancer and complete Kessler-6 and covariate data (unweighted <i>n</i> = 3,680; weighted ~ 22.2 million). SPD was defined as a Kessler-6 score ≥ 13. Weighted prevalence and multivariable logistic regression identified independent correlates.</p> Results <p>The weighted prevalence of SPD was 3.7% (95% CI, 3.0%-4.5%). SPD was higher among adults aged 18—44&#xa0;years (10.2% [5.5%-14.9%]) versus ≥ 65&#xa0;years (2.4% [1.7%-3.1%]), women (4.8% [3.5%-6.0%]) versus men (2.6% [1.7%-3.6%]), and those with Medicaid (14.4% [7.5%-21.2%]) or no insurance (14.1% [3.6%-24.5%]). SPD was also elevated among survivors with frequent loneliness (11.7% [8.9%-14.4%]), low social support (10.7% [7.8%-13.7%]), life dissatisfaction (24.0% [16.5%-31.5%]), and functional limitations (5.5% [4.3%-6.7%]). In multivariable analyses, frequent loneliness (aOR 5.46 [2.39—12.47]), low social support (2.92 [1.40—6.08]), and life dissatisfaction (3.92 [1.64—9.46]) were independently associated with SPD; odds were lower among non-Hispanic Black adults (0.28 [0.08—1.00]). Sensitivity analyses excluding psychosocial variables strengthened associations for younger age and Non-Hispanic Black race/ethnicity.</p> Conclusions <p>Serious psychological distress affected a clinically important minority of US cancer survivors and was strongly associated with psychosocial factors, including loneliness, social support, and life satisfaction.</p> Implications for Cancer Survivors <p>Integrating psychosocial assessment and targeted support into survivorship care may reduce distress and improve overall well-being.</p>