Objective This study aimed to identify key factors affecting nursing students' work ability, focusing on the roles of job demands and social support. Background High nurse turnover contributes to a global shortage, with intentions to leave the profession often forming during study years. Work ability is a well-established predictor of career mobility intentions. Design A nationwide cross-sectional survey-based study was conducted among Czech nursing students using an online self-administered questionnaire. Methods The questionnaire covered sociodemographic and anamnestic characteristics, health perceptions, workplace challenging experiences, job demand, control, and social support (JDCS) constructs, and the Work Ability Index (WAI). Results Musculoskeletal pain was prevalent: 81.3 % reported lower back pain, 68.8 % neck pain, and 52.1 % shoulder pain. The median WAI score was 39 (Range: 20–49). WAI score was moderately correlated with self-perceived health (rho = 0.531) and perceived exhaustion (rho = −0.542). Students with lower back pain (β = −1.67), upper back pain (β = −2.56), shoulder pain (β = −2.72), and neck pain (β = −2.81) reported lower WAI. Workplace bullying (β = −2.66) and discrimination (β = −2.14) further reduced WAI. While job demand (β = −0.70) lowered WAI, job control (β = 0.66) and social support (β = 0.67) improved it. Conclusions Self-perceived health and social support positively influence work ability, while perceived exhaustion, musculoskeletal pain, and workplace bullying and discrimination reduce it. Creating supportive environments and addressing health challenges may enhance retention and well-being in the young nursing workforce.