Lycopene, constituting 80-90% of the total carotenoid content present in tomatoes and tomato products, has been believed to contribute to the reduced risks of some types of cancers. Vitamin C of tomato fruits accounts for up to 40% of the recommended dietary allowance for human beings. As a result, enhancing the levels of these two health chemicals in tomato fruits may form an efficient way to improve human health conditions. In response to this opportunity, numerous investigations have been conducted to identify the factors influencing the contents of lycopene and vitamin C in tomatoes. The results demonstrate consistent differences in lycopene and vitamin C content between tomato cultivars, which can be magnified by agricultural management. A relationship has been established associating electrical conductivity (EC) and light intensity with lycopene and vitamin C content in tomato fruits. Generally, moderate EC growing conditions enhance tomato health quality; solar radiation is favourable to lycopene and vitamin C accumulation, whereas strongly intense light exposure inhibits lycopene synthesis. Temperatures beyond the optimum temperature range may inhibit lycopene biosynthesis. However, the effects of temperature on vitamin C content are not always conclusive. The effects of nutrients (N, P, K, and Ca) and water availability have also been reviewed, but results are sometimes contradictory. Up-to-date studies dealing with cultivar and agricultural management on lycopene and vitamin C contents in tomato fruits are reviewed in this chapter