(1) Background: Loss of weight is one of the practices which have been identified as key in reducing the risk of various forms of cancer. Therefore, this study is a systematic review and meta-analysis of studies related to the topic of loss of weight and risk of cancer and addresses the question, ‘does losing weight reduce the risk of cancer?’ Its purpose is to identify current high-quality evidence on such a question and synthesize such evidence before summarizing it given specific data attributes to improve decision-making processes on cancer management. (2) Methods: Research studies were identified from four main databases: PubMed, Science Direct, Google scholar, and Medline. A systematic review and meta-analysis of such studies were then conducted to reveal the most current evidence on the research topic. (3) Results: The studies showed that losing weight reduces cancer risk. Nonetheless, such intervention is not necessarily effective, especially in cases where patients may be at risk of developing cancer due to other risk factors. (4) Conclusions: The current study concludes that there is a need to implement effective interventions such as physical exercise, dietary restrictions, or both that can be effective in reducing weight to reduce the risk of cancer.