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Background and Objective: Myofascial pain syndrome (MPS) is a chronic musculoskeletal disorder characterized by the presence of trigger points. Among the treatment options, botulinum toxin injections have been investigated. The aim of this paper was to provide a review of the evidence on intramuscular botulinum toxin injections for upper back MPS. Databases and data treatment: A systematic review of the literature was performed on PubMed, Scopus, and Cochrane Library, using the following formula: (“botulinum”) AND (“musculoskeletal”) AND (“upper back pain”) OR (“myofascial pain”). Results: Ten studies involving 651 patients were included. Patients in the control groups received placebo (saline solution) injections, anesthetic injections plus dry needling, or anesthetic injections. The analysis of the trials revealed modest methodological quality: one “good quality” study, one “fair,” and the other “poor.” No major complications or serious adverse events were reported. Results provided conflicting evidence and did not demonstrate the superiority of botulinum toxin over comparators. Most of the included trials were characterized by a small sample size, low power analysis, different clinical scores, and non-comparable follow-up periods. Even if there is no conclusive evidence, the favorable safety profile and the positive results of some secondary end points suggest a potentially beneficial effect on pain control and quality of life. Conclusion: The studies currently available show conflicting results. Their overall low methodological quality does not offer solid evidence of superiority over other comparative treatments. Further studies are needed to determine the profile of patients who could benefit most from this use of injections. Significance: The randomized controlled trials included in this review compared the use of botulinum toxin to treat upper back MPS with the use of placebo or active treatments (e.g., dry needling or anesthetics), showing mixed results overall. Despite the lack of clear evidence of superiority, our study suggests that the use of botulinum toxin should not be discouraged. Its safety profile and encouraging results in pain control, motor recovery, and disability reduction make it an interesting treatment, particularly among the subset of patients with moderate to severe chronic pain and active trigger points. To support the safety and efficacy of botulinum toxin, further high-quality studies are needed.