Precision oncology is a rapidly evolving concept that holds great promise in cancer treatment. However, a cancer complexity attributed to genomic and acquired tumour heterogeneity limits treatment effectiveness and increases toxicity. These limitations refer to both systemic therapies and radiotherapy, which are two mainstays of non-invasive cancer treatment. By understanding cancer heterogeneity and utilising advanced tools to personalise treatment strategies, precision oncology has the potential to revolutionise cancer care. In this article, we review the current status of precision oncology in solid tumours, specifically focusing on the impact of tumour heterogeneity and genomic patient features on systemic therapies and radiation. We also discuss the implementation of novel tools, such as next-generation sequencing and liquid biopsies, to overcome this problem.