Measuring muscle fatigue and resistance to fatigue is a topical theme in many clinical research studies. Multi-domain approaches, including electromyography (EMG), are employed to measure fatigue in rehabilitation contexts. In particular, spectral features, such as the reduction in the median frequency, are accepted biomarkers to detect muscle fatigue conditions. However, applications of fatigue detection in clinical scenarios are still limited and with margin for improvement. One of the potential applications of such methodology in clinics concerns the evaluation of the rehabilitation after hip fracture. In this work, 20 inpatients, in the acute phase after hip fracture surgery and with lower limb weakness, performed isometric contractions with their healthy lower limb (quadriceps muscle) and their resistance to fatigue before and after 2 weeks of rehabilitation program was measured. Multi-channel EMG and Maximum Voluntary Contractions (MVC, force) were recorded on five muscle heads. We found that, after performing the same number of repetitions (repetitions pre-treatment: 19.7 ± 1.34; repetitions post-treatment: 19.9 ± 0.36; p = 0.223), MVC improved (MVC pre-treatment: 278 ± 112 N; MVC post-treatment: 322 ± 88 N; p = 0.015) after rehabilitation for most of the patients and fatigue did not change. These results suggest that higher force exertion was performed after rehabilitation, with the same level of fatigue (fatigued muscles pre-treatment: 1.40 ± 1.70; fatigued muscles post-treatment: 1.15 ± 1.59; p = 0.175) after. Results are discussed addressing the potential of multifactorial instrumental assessments for describing patients’ status and provide data for clinical decision making.