Accurate volume delineation plays an essential role in radiotherapy. Contouring is a potential source of uncertainties in radiotherapy treatment planning that could affect treatment outcomes. Therefore, reducing the degree of contouring uncertainties is crucial. The role of utilized imaging modality in the organ delineation uncertainties has been investigated. This systematic review explores the influential factors on inter-and intra-observer uncertainties of target volume and organs at risk (OARs) delineation focusing on the used imaging modality for these uncertainties reduction and the reported subsequent histopathology and follow-up assessment.An inclusive search strategy has been conducted to query the available online databases (Scopus, Google Scholar, PubMed, and Medline). 'Organ at risk', 'target', 'delineation', 'uncertainties', 'radiotherapy' and their relevant terms were utilized using every database searching syntax. Final article extraction was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Included studies were limited to the ones published in English between 1995 and 2020 and that just deal with computed tomography (CT) and magnetic resonance imaging (MRI) modalities.A total of 923 studies were screened and 78 were included of which 31 related to the prostate 20 to the breast, 18 to the head and neck, and 9 to the brain tumor site. 98% of the extracted studies performed volumetric analysis. Only 24% of the publications reported the dose deviations resulted from variation in volume delineation Also, heterogeneity in studied populations and reported geometric and volumetric parameters were identified such that quantitative synthesis was not appropriate.This review highlightes the inter- and intra-observer variations that could lead to contouring uncertainties and impede tumor control in radiotherapy. For improving volume delineation and reducing inter-observer variability, the implementation of well structured training programs, homogeneity in following consensus and guidelines, reliable ground truth selection, and proper imaging modality utilization could be clinically beneficial.