Cancer-related fatigue (CRF) is common among breast cancer (BC) survivors. In addition to aerobic training, psychoeducation, sleep education/restriction, and mindfulness-based therapies are shown to reduce CRF. This study investigates the predictive effect of hygiogenetic and salutogenetic concepts, such as autonomic regulation (aR), self-regulation (SRS) and internal coherence (ICS) along with sleep quality (PSQI) and quality of life (EORTC QLQ C30, including cognitive, emotional and physical functioning) on the success of CRF therapies. Two studies are analyzed: a pilot (CRF-1) with 36 BC patients and a follow-up study (CRF2) with 126 patients either randomized or assigned to therapy by preference. All parameters were assessed at baseline and 10 weeks post-intervention (T1), and in CRF-2 also six months later (T2), and after four years (T3). Multiple linear regression models were applied. Trait aR and ICS are shown to be significant predictors of CRF when all timepoints of the CRF-2 study are included (β = -0.170, df = 70, p < 0.001; β = -0.210, df = 70, p < 0.01) as well as when combined with data of the CRF-1 study (β = -0.144, df = 101, p = 0.001; β = -0.211, df = 101, p < 0.01). Cognitive Function showed a borderline significance only at T3 and when all CRF-2 study time measurements were combined (β = -0.073, df = 70, p < 0.05). Using data from two studies with multimodal, aerobic and combined CRF treatments, this study highlights Trait aR and ICS at baseline as long-term predictors of CRF even four years after intervention. A stable autonomic regulation including rest/activity regulation and internal coherence are predictors for therapy response of a multimodal, combination or aerobic treatment in breast cancer survivors with CRF.