Deficiencies of secondary and micronutrients (SMNs) are major causes of low maize yields in poorly responsive soils. This phenomenon minimizes the agronomic efficiency of N, P and K fertilizers and consequently result in a dwindling economic benefit associated with their use. Therefore, 18 on-farm trials were conducted in western Kenya during two cropping seasons to assess maize response to three NPK amendments; (i) N, P, K, Ca, Zn and Cu (inorganic and organic); (ii) N, P, K, Ca, Zn and Cu (inorganic) and (iii) N, P K, Zn and Cu (inorganic) and evaluate the profitability of their use compared to additions of only N, P and K fertilizers. In this set of experiments, maize response to any amendment refers to a yield increase of ≥2 t ha−1 above control and could be categorized in three clusters. Cluster 1, comprising of nine sites, maize responded to all amendments. Cluster 2, holding six sites, maize responded only to one amendment, N, P, K, Ca, Zn and Cu (inorganic). In this cluster, (2), emerging S, Mg and Cu deficiencies may still limit maize production. Cluster 3; consisting of three sites, maize responded poorly to all amendments due to relatively high soil fertility (≥17 mg P kg−1). Profitability of using NPK amendments is limited to Cluster 1 and 2 and the largest Value Cost Ratio (VCR) of 3.1 is attainable only when soil available P is below 4.72 mg kg−1. These variable responses indicate the need for developing site-specific fertilizer recommendations for improved maize production and profitability of fertilizer use in poorly responsive soils.