(1) Background: Spinal cord injury (SCI) represents a major health challenge, often leading to significant and permanent sensorimotor and autonomic dysfunctions. This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety. The objective was to analyze how eSCS contributes to the recovery of neurological functions in SCI patients. (2) Methods: We utilized the PRISMA guidelines and performed a comprehensive search across MEDLINE/PubMed, Embase, Web of Science, and IEEE Xplore databases up until September 2023. We identified studies relevant to eSCS in SCI and extracted assessments of locomotor, cardiovascular, pulmonary, and genitourinary functions. (3) Results: A total of 64 studies encompassing 306 patients were identified. Studies investigated various stimulation devices, parameters, and rehabilitation methods. Results indicated significant improvements in motor function: 44% of patients achieved assisted or independent stepping or standing; 87% showed enhanced muscle activity; 65% experienced faster walking speeds; and 80% improved in overground walking. Additionally, eSCS led to better autonomic function, evidenced by improvements in bladder and sexual functions, airway pressures, and bowel movements. Notable adverse effects included device migration, infections, and post-implant autonomic dysreflexia, although these were infrequent. (4) Conclusion: Epidural spinal cord stimulation is emerging as an effective and generally safe treatment for chronic SCI, particularly when combined with intensive physical rehabilitation. Future research on standardized stimulation parameters and well-defined therapy regimens will optimize benefits for specific patient populations.