The advent of simultaneous PET/MRI brought a large amount of possibilities in research and clinical applications into hybrid imaging. Unlike in PET/CT protocols, the MR component provides an almost unlimited number of pulse sequences and possibilities of different protocols in PET/MRI. Nevertheless, there is an imperative to reduce excessive imaging protocols to realistic clinical practice imaging acquisition. The design of a concise and indication-adapted protocol that provides an efficient workflow in a clinical reality is necessary to transform PET/MRI to a cost-effective imaging modality in addition to PET/CT. The aim of the current article is to point out the main considerations regarding workflow, imaging protocols, and image analysis in simultaneous PET/MRI system in oncology and share our thoughts and experience in acquisition optimization compared with the current literature.