Cancer is currently a leading cause of deaths worldwide and the number of new cases is growing rapidly in both, developed and developing countries. Nutritional management during and after cancer treatment affects treatment efficacy and patient quality of life (QOL). This review systemically examined the effect of oral nutritional interventions on nutritional and clinical outcomes in cancer patients. We especially focused on outcomes such as nutritional status indices, immune-associated biochemical markers, and QOL assessments to provide insights on the applicability of different outcomes. A total of 28 papers were selected for systematic review. The nutritional composition of oral nutritional supplements (ONS), outcome measures, and efficacy of the oral nutritional interventions were summarized and discussed. Most ONS contain 1 or more functional components in addition to basic nutrients. Each study used various outcome measures and significant efficacy was observed for a limited number of measures. Nutritional status indices, QOL measures, and the duration of hospital stay improved in about 40% of the studies. One or more markers of immune function and inflammatory responses were improved by ONS in 65% of the selected studies. These results suggest that appropriate use of ONS may be an ideal way to improve treatment efficacy; however, additional intervention trials are required to confirm these findings.