Background Chemotherapy-related toxicity affects the quality of life (QOL) of patients with cancer. Measuring the QOL in breast cancer (BC) patients has been the focus of clinical practices and research in recent decades. This study aimed to assess the impact of BC medications on QOL of Sudanese patients with BC. Methods A cross-sectional study was conducted in Khartoum Oncology Hospital, Sudan, from November 2020 to March 2021. All patients diagnosed with BC were included in the study. QOL was assessed using the European Organization for Research and Treatment of Cancer quality of life (EORTC QLQ-C-30) and breast cancer supplementary module (QLQ-BR23). ANOVA, independent t-test and logistic regression analysis were used to assess the association between variables. Results Two hundred patients were enrolled in the study, with a mean age of 50 ± 11.7 years. 52.5% of the patients were on a conventional therapy whereas 40.5% and 7% received hormonal and HER2-targeted therapies, respectively. In QLQ-C30 scale, the global health-QOL status score was (53.2 ± 1.9), with 54.0% of patients having poor global health-QOL status. In the functional scale, the cognitive functioning was the highest score (80.7 ± 1.8). In QLQ-C30 symptom scale, the most distressing issue was financial difficulties (63.7 ± 2.9). In QLQ-BR23 scale, body image scored the worse functioning (47.7 ± 2.7), with 54.5% of patients having poor QOL. In QLQ-BR23 symptoms scale, “being upset by hair loss” was the highest disturbing symptom (62.1 ± 3.3), with 68.6% of patients having poor QOL. Global health status (P = 0.000), social (P = 0.000), emotional (P = 0.002) and role functioning (P = 0.000) were significantly higher in patients taking HER2-targeted or hormonal therapy compared to conventional therapy. The level of symptomatology was significantly low in patients taking HER2-targeted therapy or hormonal therapy (P = 0.000) than those on conventional therapy. Hormonal (OR = 3.7, p = 0.01) and HER2-targeted therapies (OR = 10.2, p = 0.04 ) were positive predictors of QOL. Conclusion BC survivors in Sudan had a low QOL/global health status. Hormonal and HER2-targeted therapies were predictors of good QOL.