Purpose As a subjective symptom, cancer-related fatigue is assessed via patient-reported outcomes. Due to the inherent bias of such evaluation, screening and treatment for cancer-related fatigue remains suboptimal. The purpose is to evaluate whether objective cancer patients’ hand muscle mechanical parameters (maximal force, critical force, force variability) extracted from a fatiguing handgrip exercise may be correlated to the different dimensions (physical, emotional, and cognitive) of cancer-related fatigue. Methods Fourteen women with advanced breast cancer, still under or having previously received chemotherapy within the preceding 3 months, and 11 healthy women participated to the present study. Cancer-related fatigue was first assessed through the EORTC QLQ-30 and its fatigue module. Fatigability was then measured during 60 maximal repeated handgrip contractions. The maximum force, critical force (asymptote of the force-time evolution), and force variability (root mean square of the successive differences) were extracted. Multiple regression models were performed to investigate the influence of the force parameters on cancer-related fatigue’s dimensions. Results The multiple linear regression analysis evidenced that physical fatigue was best explained by maximum force and critical force ( r  = 0.81; p  = 0.029). The emotional fatigue was best explained by maximum force, critical force, and force variability ( r  = 0.83; p  = 0.008). The cognitive fatigue was best explained by critical force and force variability ( r  = 0.62; p  = 0.035). Conclusion The handgrip maximal force, critical force, and force variability may offer objective measures of the different dimensions of cancer-related fatigue and could provide a complementary approach to the patient reported outcomes.