The proper management of treated agricultural wastes (e.g., composts) contributes to the protection of water and soil quality by reducing the use of chemical fertilizers, lowering leachate, and protecting renewable and nonrenewable resources. Natural zeolites, particularly clinoptilolite, can be used in agriculture to improve soil quality and increase yields due to their unique properties. The objective of the study was to test the effects of the co-addition of compost, zeolite and ammonium-based fertilizer on the Above-ground Fresh Weight (AFW) of lettuce (Lactuca sativa L.), leaf nutrients and soil fertility. To this aim, a soil pot experiment was carried out at the Department of Soil Science of Athens, which is located in the region of Attica, in the area of central Greece. Two levels of olive compost originated from olive leaves (0% and 10% v/v), three levels of zeolite (0%, 2%, and 5% w/w) and two levels of chemical fertilization (no fertilization and NPK fertilization) were combined. Furthermore, two different soils were introduced, one moderately acidic (pH = 5.6) and sandy loam in texture (Ac-LT), and the other slightly alkaline (pH = 7.7) and sandy clay in texture (Al-HT). Results showed that the response of lettuce yield to chemical fertilization and zeolite application is soil type-dependent, whereas compost application significantly improved AFW in both soil types. The availability of macronutrients (P, K, and Na) in the soil, as well as their concentration in leaves, were significantly increased by NPK fertilization in most cases. Conversely, the impact of inorganic fertilization on DTPA extractable micronutrients and leaf micronutrient contents was found to be associated with the type of soil. The study recorded a significant reduction in available Fe, Cu, and Mn in AL-HT soil, whereas DTPA-Mn and -Zn were significantly enhanced in Ac-LT soil. Comparable patterns were also documented for the micronutrient concentration in leaves. In most cases, compost application had significant and beneficial effects on plant nutrients. On the contrary, different responses of soil properties to compost addition were registered. The main effect of compost treatment on soil pH, EC, SOM, total N, and available P was significant and positive in both soil types, except for pH and EC in Al-HT soil. On the other hand, exchangeable K and Na were significantly reduced by compost. Zeolite substantially increased the availability of P, K, and Na in soil and plants, whereas the concentrations of DTPA-extractable micronutrients and leaf macronutrients were largely unaffected. In addition, the results of our study indicated that co-additions of organic and inorganic amendments did not yield any significant impact on the lettuce yield, leaf nutrient content and soil fertility. It is suggested that the degree of changes in main soil properties (e.g., pH, EC, SOM) as a result of amendment application as well as the interaction of the amendments with nutrient availability are strongly related to soil type.