Lebanese cancer patients are facing a war on two fronts, between the COVID-19 pandemic and one of the most severe financial crises globally in recent times. This multicentric cross-sectional study was conducted, aiming to analyse challenges and perspective of this particularly vulnerable population. A questionnaire was prepared to assess socio-demographic data, challenges faced during the pandemic, perspectives concerning cancer and COVID-19, a scale was also validated to assess knowledge level regarding COVID-19 in this population. Patients were interviewed in chemotherapy units from four different private and public hospitals in Lebanon during December 2020 and March–June 2021. In total, 272 patients were interviewed (median age, 57 years, range, 22–90 years). Concerning salary during the pandemic, it changed negatively (45.6%), or did not change (7.7%), while 46.7% of participants did not work. Some challenges such as transportation problems (39%), inability to reach their physician by phone (16.9%), deferral of chemotherapy dates (31.6%), difficulty finding chemotherapy medications (49.6%) were more likely to be reported by patients receiving chemotherapy in public compared to private hospitals (p < 0.01 for each). Other challenges include not being able to find non-cancer-related medications (71.3%), this challenge being increased when comparing December 2020 with March–June 2021 (p < 0.02). Using a multivariate analysis, the best predictor for increased knowledge about COVID-19 was higher levels of education (p < 0.001). In conclusion, this study shows that cancer patients in Lebanon are facing many challenges that complicate different aspects of health. Perspective and challenges of these patients must be taken into consideration in order to deliver better care to our patients in these unprecedented times.