Premarital screening is a vital preventive health measure to identify genetic and chronic conditions that may affect couples after marriage. This study investigated the predictors of premarital screening uptake among male and female youths in Alimosho Local Government Area, Lagos State, Nigeria. Using a descriptive cross-sectional design, data were collected from 200 respondents through structured questionnaires on socio-demography, awareness, and barriers to screening uptake. Data was analyzed using Descriptive and inferential statistics, chi-square, and logistic regression. Findings revealed an awareness level of 81%, while only 51.5% had undergone screening, and a significant barrier of finance among 52.5% of respondents. Gender differences revealed that women are more likely to support screening, with Awareness as an essential predictor of screening uptake among those with higher education, aged 21-25 years. The study concluded that increasing public health education, addressing financial barriers, and promoting gender-inclusive awareness campaigns are essential for improving premarital screening participation.