Sugarcane grown in sandy soils (≤10% clay) is prone to drought stress and pest infestations, including nematodes, yellow sugarcane aphids (YSAs), and thrips. A granular soil-applied product containing oxamyl and imidacloprid is commonly used for pest control, with imidacloprid also reported to alleviate stress responses in various crops. This study by the South African Sugarcane Research Institute aimed to evaluate the yield response of different sugarcane varieties to this product across ratoon crops and to assess its cost-effectiveness under varying stress indices. Varieties were grown under treated and untreated conditions, and their performance was assessed relative to a calculated stress index (defined as the average yield of untreated controls as a percentage of the modelled yield potential). There was a statistically significant inverse correlation between the percentage yield increase (tch) and the crop stress index (Pearson’s r = –0.273; p < 0.01; n = 131), suggesting greater yield gains in more stressed environments. Ratoon crops with stress indices below 75% showed the most notable yield improvements. For example, N60 (North Coast, Blythedale) recorded a 109% increase and N51 (North Coast, Umhlali) 61%, and N62 (Midlands South) showed an increase of 71%. Additionally, gross margin differences (calculated using the July 2024 RV price) were generally positive in treated crops with <75% stress index, and most varieties under marginal and unstressed conditions also saw economic benefits. Negative gross margins observed in some crops may reflect unmeasured stressors affecting the yield response. These findings highlight the value of the strategic application of oxamyl/imidacloprid, particularly in stressed environments, and offer practical guidelines for variety selection and pest management in sandy soils.