Hippocrates, the "Father of Rhinology," provided detailed descriptions of nasal polypoidal tumors and nasal complex from 460-370 B.C. His writings are the earliest known sinus anatomy, with anatomists studying primates and mammals focusing on paranasal air sinuses. This systematic review explores the link between anatomical variations in the sinonasal region and sinus pathology, providing a comprehensive understanding of the prevalence, types, and clinical implications, thereby aiding clinicians in making informed decisions and improving patient outcomes. A thorough search of PubMed, Google Scholar, Research Gate and PRISMA guidelines were used to perform this review, with subjects related to the study's title as the primary search criteria. We used the following search terms: nasal blockage, paranasal sinus, sinus pathology, and nasal-respiratory complex. Anatomical variations in the ostiomeatal complex, found in 83.5% of cases, significantly impact sinus drainage and ventilation, leading to sinus pathology. Variations like deviated nasal septum, concha bullosa, and agger nasi cells obstruct mucus and air flow, causing sinusitis. Studies show a clear association between anatomical variations and chronic sinusitis, highlighting the importance of considering these variations when evaluating patients with sinus pathology. Nasal polyps are another common pathology associated with anatomical variations in the sinonasal region. Sinusitis is the most common condition affecting the nose and paranasal sinuses, which are affected by trauma, tumors, and sphenoid sinuses. Staphylococcus bacteria, found on skin and nasal cavities, can infect people. Sinonasal disease encompasses a range of illnesses, from inflammatory to malignant, and is the fifth leading cause of antibiotic use and the highest frequency across all age groups. Research indicates a correlation between anatomical variations in the sinonasal area and sinus pathology, particularly in patients with chronic rhinosinusitis. Careful assessment and CT are crucial for identifying and treating these variations. Further research is needed to fully understand the clinical implications of these variations, as they can significantly impact sinus pathology and the management of sinus conditions.