Neuroimaging of cerebral neoplastic lesions and post-radiation necrosis (PRN) presents significant challenges due to their overlapping features, making differentiation difficult. The use of various imaging modalities in association with radiation therapy introduces potential risks and prognostic variations that can affect lesion physiology. Patients who undergo radiation treatment inevitably experience changes influenced by factors such as radiation dose, brain volume, and tumor fraction size. Additionally, vascular injury and the inflammatory response associated with radiation contribute to alterations observed in neuroimaging. This literature review aims to provide a comparative overview of imaging studies to highlight the optimal modality to distinguish between PRN and tumor recurrence. The imaging modalities assessed included dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) MR-perfusion, MR-spectroscopy, intravoxel incoherent motion (IVIM) perfusion, and nuclear medicine studies, including 18F-fluoro-ethyl-1-tyrosine positron emission tomography (18F-FET PET) and 11C-methionine PET (11C MET-PET). The improvement of diagnostic accuracy in multimodal imaging must be further investigated to improve clinical patient management and outcomes of tumor reoccurrence.