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Background Cancer treatment itself and particularly chemotherapy unavoidably affects host cells, often producing a variety of side effects, e.g., nausea, vomiting, diarrhea, and fever, and further decreases in appetite, physical activity, and body weight. These effects, combined with biochemical and histological injuries to major organ systems, may result in a profound nutritional insufficiency. This study aimed to determine the nutritional status of patients receiving chemotherapy. Methods A prospective study was conducted among 64 adults newly diagnosed cancer patients of various sites, admitted to the Oncology Department at European Gaza Hospital (EGH), and scheduled for the first cycle of chemotherapy. The nutritional status of each patient was assessed using the Subjective Global Assessment (SGA) and anthropometry before commencing the first cycle of the chemotherapy regimen (pre) and after completing the chemotherapy regimen (post). Additionally, biochemical and dietary intake assessments were also performed. Results Nutritional status worsened after the completion of a chemotherapy regimen. It has been found that 80.3% of patients suffered from malnutrition (moderate and severe) after the completion of the chemotherapy regimen based on SGA in comparison to 35.9% who were malnourished before commencing the first cycle of chemotherapy. The results reported the presence of a functional vitamin B12 deficiency, such that there is a drastic reduction in serum vitamin B12 levels (355.0(IQR 115.0) to 219.0(IQR 177.0) pg/mL, P  < 0.001), accompanied by a significant increase in it is related metabolites methylmalonic acid (MMA) (3.9(IQR 3.0) to 49.7(IQR 32.0) ng/mL, P  < 0.001), and homocysteine (Hcy) (3.90(IQR 0.85) to 12.60(IQR 7.05) ng/mL, P  < 0.001) after the completion of chemotherapy regimen. Dietary intake in terms of macronutrients and micronutrients changed significantly after the completion of chemotherapy regimen. Conclusions Cancer patients who received chemotherapy were at risk of malnutrition hence it is a wise practice to conduct thoroughly and deep nutritional assessment for each patient at the baseline, during treatment and after the completion of chemotherapy regimen.