Precision oncology is a novel personalized treatment method for cancer. It delves into the molecular composition of an individual’s tumor and provides therapies based on that information. This method is highly specific in nature and incorporates targeting specific genetic mutations or alterations found across many cancer types. Instead of limiting treatment to the killing of rapidly dividing cancer cells, precision oncology relies on molecular profiling of an individual’s tumor; hence this therapy is more personalized. The milieu surrounding the tumor, known as the tumor microenvironment, provides many crucial keys to tumor growth, pattern, and development. Recent advances have initiated the incorporation of artificial intelligence and machine learning in cancer treatment strategies, due to which greater amounts of data can be handled. Patterns and behavior found within the tumor microenvironment can also be identified. Now, appropriate treatment plans can be selected and modified as needed to avoid adverse reactions. Management of cancer requires minimizing side effects and maximizing the quality of life. Quality of life is an important factor in precision oncology because it is a more personalized method to improve the overall well-being of patients. It makes it easier to navigate the mechanisms of drug interaction and resistance, ultimately improving outcomes for patients and their quality of life as well. Helping patients comprehend and accept precision oncology-based treatment will be difficult because of the ongoing applications of advanced decision-making tools that allow physicians to choose the most suitable treatment approach. This chapter provides an overview of precision oncology, its mechanisms, therapies, recent advances, and how it correlates with the quality of life of an individual suffering from cancer. Many challenges lie ahead of us before cancer patients are willing to choose and trust precision oncology over traditional cancer treatment methods.