Background: Post-COVID-19 syndrome (PCS) may affect a substantial proportion of patients who have had COVID-19. The rehabilitation program might improve the physical capacity, functioning of the cardiopulmonary system, and mental conditions of these patients. This study aimed to investigate the effectiveness of personalized rehabilitation in patients with PCS according to gender. Methods: Adults who underwent a 6-week personalized PCS rehabilitation program were enrolled in a prospective post-COVID-19 Rehabilitation (PCR-SIRIO 8) study. The initial visit and the final visit included the hand-grip strength test, the bioimpedance analysis of body composition, and the following scales: modified Borg’s scale, Modified Fatigue Impact Scale (MFIS), Functioning in Chronic Illness Scale (FCIS), modified Medical Research Council (mMRC) dyspnea scale, and tests: 30 s chair stand test (30 CST), Six-Minute Walk Test (6MWT), Short Physical Performance Battery test (SPPB)e. Results: A total of 90 patients (54% female) underwent the rehabilitation program. Rehabilitation was associated with an increase in skeletal muscle mass (24.11 kg vs. 24.37 kg, p = 0.001) and phase angle (4.89° vs. 5.01°, p = 0.001) and with a reduction in abdominal fat tissue volume (3.03 L vs. 2.85 L, p = 0.01), waist circumference (0.96 m vs. 0.95 m, p = 0.001), and hydration level (83.54% vs. 82.72%, p = 0.001). A decrease in fat tissue volume and an increase in skeletal muscle mass were observed only in females, while an increase in grip strength was noticed selectively in males. Patients’ fatigue (modified Borg’s scale, MFIS), physical capacity (30 CST, 6MWT), balance (SPPB), dyspnea (mMRC), and functioning (FICS) were significantly improved after the rehabilitation regardless of gender. Conclusions: Personalized rehabilitation improved the body composition, muscle strength, and functioning of patients diagnosed with PCS. The beneficial effect of rehabilitation on body composition, hydration, and phase angle was observed regardless of gender.