Artificial intelligence (AI) refers to a field of computer science aimed to perform tasks typically requiring human intelligence. Currently, AI is recognized in the broader technology radar within the five key technologies which emerge for their wide-ranging applications and impact in communities, companies, business, and value chain framework alike. However, AI in medical imaging is at an early phase of development, and there are still hurdles to take related to reliability, user confidence, and adoption. The present narrative review aimed to provide an overview on AI-based approaches (distributed learning, statistical learning, computer-aided diagnosis and detection systems, fully automated image analysis tool, natural language processing) in oncological hybrid medical imaging with respect to clinical tasks (detection, contouring and segmentation, prediction of histology and tumor stage, prediction of mutational status and molecular therapies targets, prediction of treatment response, and outcome). Particularly, AI-based approaches have been briefly described according to their purpose and, finally lung cancer—being one of the most extensively malignancy studied by hybrid medical imaging—has been used as illustrative scenario. Finally, we discussed clinical challenges and open issues including ethics, validation strategies, effective data-sharing methods, regulatory hurdles, educational resources, and strategy to facilitate the interaction among different stakeholders. Some of the major changes in medical imaging will come from the application of AI to workflow and protocols, eventually resulting in improved patient management and quality of life. Overall, several time-consuming tasks could be automatized. Machine learning algorithms and neural networks will permit sophisticated analysis resulting not only in major improvements in disease characterization through imaging, but also in the integration of multiple-omics data (i.e., derived from pathology, genomic, proteomics, and demographics) for multi-dimensional disease featuring. Nevertheless, to accelerate the transition of the theory to practice a sustainable development plan considering the multi-dimensional interactions between professionals, technology, industry, markets, policy, culture, and civil society directed by a mindset which will allow talents to thrive is necessary.