Purpose: Cancer-related fatigue (CRF) is the most reported side effect of cancer and its treatments. Mechanisms of CRF are multidimensional, including neuromuscular alterations leading to decreased muscle strength and endurance (i.e., fatigability). Recently, exercise fatigability and CRF have been related, while fatigability mechanisms remain unclear. Traditionally, fatigability is assessed from maximal voluntary contractions (MVC) decrease, but some authors hypothesized that the rate of force development (RFD) determined during a rapid contraction could also be an interesting indicator of functional alterations. However, to our knowledge, no study investigated RFD in cancer patients. The purpose of this study was to determine whether RFD, fatigability amplitude, and etiology are different between fatigued and non-fatigued cancer patients. Methods: Eighteen participants with cancer, divided in fatigued or non-fatigued groups according their CRF level, completed a 5-min all-out exercise in ankle plantar flexor muscles composed of 62 isometric MVC of 4 s with 1 s rest, to assess fatigability amplitude as the force-time relationship asymptote (FA). Before and after exercise, fatigability etiologies (i.e., voluntary activation (VA) and evoked forces by electrical stimulation (Db100)) were assessed as well as RFD in 50 and 100 ms (RFD50 and RFD100, respectively) during rapid contractions. Results: FA is significantly lower in fatigued group. Significant differences were found between pre- and post-exercise VA, Db100, RFD50, and RFD100 for both groups, with no statistical difference between groups. Conclusion: During treatments, fatigability is higher in fatigued patients; however, the mechanisms of fatigability and RFD alterations are similar in both groups. Trial registration: ClinicalTrials.gov, NCT04391543, May 2020.