Background/Objectives: Abnormal blood pressure (BP) in youth is strongly linked to genetic predisposition, particularly involving lipid metabolism genes. However, little is known about whether such polymorphisms affect ambulatory BP (ABP) parameters and whether other factors modify the associations in youth populations. Methods: A total of 510 medical students from a university in Changsha were included. Multivariable linear regression and logistic regression models were used to analyze the association between sterol regulatory element-binding protein cleavage-activating protein (SCAP) gene polymorphisms and ABP parameters among youth. Results: After adjusting for age, sex, BMI, ethnicity, monthly household income per capita, salt intake habits, fruit and vegetable intake frequency, smoking, drinking, history of hypertension and waist circumference, carriers of the A allele of rs76558868 had higher daytime systolic blood pressure (SBP) than G allele carriers (β = 1.55, SE = 0.77, p = 0.046, corrected p = 0.092). A significant interaction between rs12487736 and sex on 24 h SBP (pinteraction = 0.023) and daytime SBP (pinteraction = 0.048) levels was found. In males, the CC genotype carriers had elevated 24 h SBP (β = 3.53, SE = 1.36, p = 0.010, corrected p = 0.020) and daytime SBP (β = 3.18, SE = 1.53, p = 0.040, corrected p = 0.080) levels compared to TC/TT genotype carriers, whereas no significant association was found in females. In addition, we also noted an interaction between rs76558868 and sex on 24 h SBP (pinteraction = 0.016), nighttime SBP (pinteraction = 0.027) and nighttime diastolic blood pressure (DBP) (pinteraction = 0.025) levels; the A allele carriers had significantly higher 24 h SBP (β = 2.02, SE = 0.84, p = 0.018, corrected p = 0.036), nighttime SBP (β = 2.64, SE = 0.98, p = 0.008, corrected p = 0.016) and DBP levels (β = 1.65, SE = 0.63, p = 0.009, corrected p = 0.018) compared to G allele carriers among males, but not in females. Conclusions: An interaction between SCAP gene polymorphisms and sex was observed for ABP parameters among college students. These findings provide insights for future targeted early hypertension prevention and personalized health management strategies.