Introduction: Chest pain is one of the most common and high-risk presentations in the emergency department (ED), necessitating timely and accurate evaluation to prevent adverse cardiovascular outcomes. Coronary Computed Tomography Angiography (CCTA) has emerged as a promising non-invasive modality with high sensitivity (90–100%) and a negative predictive value (98–100%) for ruling out significant coronary artery disease (CAD), as evidenced by trials such as ROMICAT II and ACRIN-PA. Despite its expanding role in ED triage, further evaluation of its impact on patient-centered outcomes is essential. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Studies published between January 2010 and June 2025 were identified from PubMed, Embase, and the Cochrane Library. Eligible studies included randomized controlled trials and prospective cohort studies assessing CCTA in ED patients with suspected acute coronary syndrome (ACS), compared with alternative diagnostic strategies, and reporting outcomes, including diagnostic accuracy, time to diagnosis, ED discharge rates, hospital admissions, and cost-effectiveness. Results: Twenty-three studies comprising over 60,000 patients were included. CCTA in low- to intermediate-risk patients significantly reduced diagnostic time (up to 54%), increased early ED discharges, and lowered unnecessary admissions. It consistently demonstrated excellent diagnostic performance, with pooled sensitivity ≥90% and near-perfect negative predictive value. Economic evaluations showed reduced costs due to shorter ED stays and less downstream testing. Challenges included radiation exposure, contrast use, and incidental findings. Conclusions: CCTA enhances ED efficiency and safety in ACS evaluation, offering accurate CAD exclusion and resource optimization. Future studies should explore its long-term cost-effectiveness and integration into high-sensitivity troponin protocols.