Papaya is a crop that is nowadays found in many tropical and subtropical regions. There is firm evidence that it responds very favorably to a high soil fertility and sufficient water supply. If such conditions are realized, very high crop yields appear to be possible. Therefore, this chapter considers the diagnosis of soil fertility from the scope of requirements of Carica papaya L. for high yield conditions. Recommendations are given for fertilization rates of the main nutrient elements N, P, K, Ca, and Mg. Additionally, nutrient deficiencies and their diagnosis are discussed with the use of three approaches: visual symptoms, the sufficiency range method, and an alternative method based on the dilution effect concept. The requirements for obtaining high yields are large nutrient application rates at water contents of soil that are close to field capacity. This combination is difficult to accomplish without adverse environmental effects, as drainage of soil water that has large nutrient concentrations is likely under these conditions. For such intensive agriculture, water and nutrient management may benefit from modeling, if it is properly supported by experimental evidence. The QUEFTS model has been developed to account for the synergistic effects of different nutrients that each may become limiting for yields. Relatively simple root zone models consider the main features of water and fertilizer dynamics and support management in a relatively practical way. More complex and demanding distributed models are nowadays rapidly developing with regard to capabilities and may help to recognize crucial gaps in knowledge. Each of these models can help the identification of trade-offs between optimum growth conditions and minimum adverse environmental effects.