Stroke remains the leading cause for lasting disability and death globally. Two frequent proinflammatory cytokine variants in the IL-10 and IL-1 beta genes, rs16944 T/C and rs1800896 G/A, may be major candidate gene loci impacting ischemic stroke vulnerability. The present case-control research aims to establish a link between both of these polymorphisms and ischemic stroke risk in the Egyptian population. The study demonstrates that the TC genotype, over dominant (TT + CC vs. TC) and dominant models (TC + CC vs. TT), exhibited greater prevalence among stroke groups as compared to the healthy group. Regarding IL-10, GA genotype, A allele, over dominant (GG + AA vs. GA), and dominant (GG vs. GA + AA) genotyping models in patients, they show highly significant differences from controls that increased the risk of stroke. Stroke patients with higher cholesterol, LDL, SBP, DBP, and lower HDL levels were more likely to develop stroke. The study found no significant link between genetic polymorphisms and smoking, gender, diabetes, or hypertension in stroke patients, except for the IL-1 beta heterozygous TC and dominant model, which was associated with troubles in chewing and swallowing and consciousness issues in the patients. Only troubles in chewing and swallowing manifestations were associated with the IL-10 variant. The rs16944 and rs1800896 polymorphisms differ substantially between groups, providing a more definite outcome for the Egyptian population and IS. The results validate the utilization of the rs16944 T/C and rs1800896 G/A variations in stroke prediction for Egyptians.