Research investigates how male and female college athletes react to strength and conditioning programs. This paper evaluates the impact of biological elements including muscle mass density and hormonal composition along with mental components including inspirational drive perception and performance awareness on shifting training success for athletic individuals of either sex. Men commonly achieve better results in muscle mass development because their higher testosterone creates improved strength gain potential yet women show different physical growth speeds and demonstrate superior physical flexibility at the same time. The research study based on primary data analysis for determine the overall research used Smart PLS Algorithm Model between the gender differences in response to strength and conditioning programs. Research demonstrates that individualized strength and conditioning programs need specific adjustments based on natural sex-based physiological differences which improve athletic performance while reducing safety risks. The knowledge of gender-specific responses enables strength and conditioning programming to produce better outcomes for male and female athletes who strive to achieve their best athletic level. Overall result found that directly link of gender differences in response to strength and conditioning programs.