A prospective cohort study investigated factors influencing return to work (RTW) in young and middle-aged stroke patients, with an emphasis on psychological resilience. Of the 131 patients, 51.8% returned to work 6 months after the incident. Higher psychological resilience as measured by the CD-RISC-10 scale was independently associated with a higher likelihood of RTW (aOR per 1 point: 1.149; 95% CI: 1.088–1.213; p < 0.001). Monthly income ≥ CNY 8,000 increased the odds of RTW (aOR: 2.568; 95% CI: 1.397–4.797). Older age (1-year aOR: 0.949; 95% CI: 0.917–0.982; p = 0.003) and higher NIHSS score (1-point aOR: 0.818; 95% CI: 0.734–0.91; p < 0.001) were negatively associated with RTW. A comprehensive model including clinical, socioeconomic, and psychological factors achieved AUC = 0.873 (95% CI: 0.830–0.916), significantly outperforming models without psychosocial factors. The authors recommend evaluating psychosocial resources and implementing early interventions for patients with low resilience.