Artemisinin-based combination therapies (ACTs) are the cornerstone of treatment for uncomplicated Plasmodium falciparum malaria in Angola. The Ministry of Health conducts therapeutic efficacy studies (TES) at sentinel sites to monitor treatment effectiveness and detect emerging antimalarial drug resistance. This study systematically reviewed the therapeutic efficacy and safety of ACTs used in Angola from 2006 to December 2025. A systematic literature search was conducted in PubMed to identify clinical studies evaluating the efficacy and safety of ACTs, including artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisininpiperaquine (DP) and artesunate-pyronaridine (ASPY), for the treatment of uncomplicated P. falciparum malaria in Angola. Of 913 records identified, seven studies from Bengo, Benguela, Luanda, Lunda Sul, Uíge, and Zaire met the inclusion criteria. ACTs showed high therapeutic efficacy, with PCR-corrected adequate clinical and parasitological response (ACPR) generally exceeding 90% through 42 days of followup. However, AL efficacy was below 90% in Zaire in 2013, 2015, Lunda Sul in 2019, and Bengo in 2021, whereas AS-AQ and DP consistently maintained high efficacy. Molecular surveillance showed no evidence of established artemisinin resistance, although markers potentially associated with reduced lumefantrine susceptibility warrant continued monitoring. Adverse events were predominantly mild and transient. ACTs remain effective and well tolerated for uncomplicated P. falciparum malaria in Angola. Nevertheless, recurrent reductions in AL efficacy at specific sentinel sites highlight the need for sustained therapeutic efficacy and molecular surveillance through regular TES to enable early detection of emerging antimalarial resistance and inform national treatment policies.