Cardiac amyloidosis has gained increasing attention in recent years due to substantial advancements in diagnostic techniques and treatment options. Among the most notable developments in this field is the approval of tafamidis by the U.S. Food and Drug Administration in May 2019 for treating transthyretin amyloid cardiomyopathy (ATTR-CM). This marked a pivotal step forward in managing this complex condition. This systematic review aimed to comprehensively analyze the efficacy of tafamidis in treating ATTR-CM and determine its broader applications, with a focus on its impact on patient outcomes, optimal dosing strategies, and side effect profiles. We strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, ensuring that the methodology was transparent and rigorous. This review involved an extensive search of multiple databases, including PubMed and Google Scholar, for relevant articles published between January 1, 2014 and January 9, 2024. After a comprehensive screening and quality assessment process, 16 high-quality articles were identified and included in the final analysis. These articles provided abundant data on the clinical outcomes associated with tafamidis use in ATTR-CM. The findings of our review highlight the transformative role of tafamidis in the treatment of ATTR-CM. The drug not only improves the quality of life of patients by significantly alleviating symptoms but also markedly reduces hospitalization rates and all-cause mortality. Tafamidis showed an impressive safety profile across different dosage levels, representing a key therapeutic option. As the use of tafamidis continues to expand in clinical practice, its potential to improve short- and long-term outcomes in patients with ATTR-CM becomes increasingly evident.