Nutrition therapy aims to prevent weight loss and its health consequences in patients with cancer. The aim of this study was to assess Greek patients’ adherence to the ESPEN guidelines for oncology patients and its prospective effect on their body weight (BW) and nutritional status. In total, 152 patients with cancer were recruited from the Attikon University Hospital, Greece, and provided data in 2019 (baseline) and 2020 (follow-up) (drop-out rate = 28.3%). Nutritional status was assessed with the PG-SGA questionnaire. Patients were categorized based on whether they adhered at least to the minimum ESPEN-recommended intakes of energy (≥25 kcal/kg/day) or protein (≥1.0 g/kg/day) or not. On average, patients did not adhere to ESPEN guidelines for energy and protein intake. Most patients meeting the minimum recommendations had an improvement of their nutritional status at follow-up and increased their BW compared to those not meeting them. All patients with head, neck, and spinal cancer who met the minimum recommendations for energy intake improved their nutritional status at follow-up. This study showed that consuming at least the minimum amounts of protein and energy recommended by ESPEN may prevent from weight loss and improve nutritional status; however, the exact amounts need to be personalized.