We carried out this study to evaluate the efficiency of watermelon production in Cai Rang district, Can Tho city, Vietnam. We collected production data from 40 watermelon farming households in the studied area through face-to-face interviews. This study used several methods, including descriptive, cost-benefit analysis, and multiple variable regression analysis. The research results showed that watermelon farming is an effective agricultural production. The average watermelon yield per 1,000 m² crop^-1 is about 3,193.5 kg, the lowest is 2,500 kg, and the highest is 5,000 kg. The total cost of watermelon cultivation per 1,000 m² crop^-1 ranged from 3,215,000 VND to 11,813,000 VND and averaged 7,405,440 VND. Profits ranged from 600,000 to 9,005,000 VND 1,000 m^-2 crop^-1 and averaged 4,515,600 VND 1,000 m^-2 crop^-1. In general, watermelon production is positive and financial efficiency achievement. The results of the regression analysis of watermelon yield depend on several factors, such as household leaders’ education level, household leaders’ production years, the cost of pesticides, and other factors that have not been included in the model. In which household leaders’ education level, household leaders’ production years, and cost of pesticides are positively correlated with productivity. Profits in watermelon farming of farmers depend on factors including land rental cost, fertilizer cost, harvesting cost, selling price, and watermelon yield.