Background <p>Life satisfaction is a key patient-reported outcome in psychosocial oncology. Yet, how health literacy, nutritional behavior, eating-related symptoms, weight changes, and CAM use together influence life satisfaction remains poorly understood.</p> Methods <p>We conducted a multicenter cross-sectional survey of 316 German oncology patients, assessing life satisfaction (L-1), health literacy, current food intake, eating-related symptoms, dietary frequency, weight change and CAM use. Analyses included descriptive statistics, Spearman correlations, nonparametric tests, and multivariate regression.</p> Results <p>Subjective health status emerged as the strongest independent predictor of life satisfaction. Higher food intake and fewer eating-related symptoms were also beneficial. Moderate unintentional weight loss (below a high threshold) was associated with somewhat higher self-perceived life satisfaction, whereas more pronounced weight loss (&gt; 10&#xa0;kg) related to lower life satisfaction. Health literacy showed a modest correlation with life satisfaction in unadjusted analyses, but lost independent significance in multivariate models, suggesting mediation via other factors. Complementary and alternative medicine use was not associated with life satisfaction. The final predictive model explained about 35.1% of the variance in life satisfaction.</p> Conclusion <p>These findings suggest that subjective health perceptions and nutritional factors are central drivers of life satisfaction in cancer patients, whereas the effect of health literacy appears to be mediated indirectly. The results support a holistic, patient-centered approach addressing subjective health, nutrition, and health literacy to improve psychosocial outcomes and life satisfaction.</p>