Abstract: China’s sugarcane industry faces the dual constraints of seasonal drought and insufficient soil fertility. Optimizing drip fertigation patterns is of great significance for improving sugarcane yield and production sustainability. This study used newly planted and ratoon sugarcane as experimental materials and adopted a two-factor randomized block design with different irrigation and fertilization levels. Three irrigation levels were set: I₅₀ (800 m³/hm²)、I₇₅ (1200 m³/hm²)、I₁₀₀ (1600 m³/hm²) and three fertilization levels: F₅₀ 180 kg(N)/hm²+90 kg(P₂O₅)/hm²+60 kg(K₂O)/hm²、F₇₅ 270 kg(N)/hm²+135 kg(P₂O₅)/hm²+90 kg(K₂O)/hm²、F₁₀₀ 360 kg(N)/hm²+180 kg(P₂O₅)/hm²+120 kg(K₂O)/hm² constituting 9 drip fertigation treatments. Meanwhile, three control treatments were established: no fertilization (CK₀), conventional fertilization (CK₁) and drip irrigation with conventional fertilization (CK₂). Main agronomic traits, yield, quality and economic benefits were determined to screen the optimal drip fertigation regime using entropy weight-grey relational analysis. The result showed that in newly planted sugarcane, tillering rate of F₁₀₀ treatments was significantly higher than that of CK₁ and CK₂ treatments, while millable stalk number of I₇₅F₁₀₀, I₁₀₀F₇₅ and I₁₀₀F₁₀₀ treatments in both newly planted and ratoon sugarcane significantly exceeded CK₁ treatment. Compared with CK₁ treatment, F₁₀₀ treatment significantly increased the cane yield by 13.94%−17.11% in newly planted sugarcane and 10.77%−22.17% in ratoon sugarcane. Both newly planted and ratoon sugarcane had the highest sucrose content under CK₀ treatment, and sucrose yield across all treatments followed the same trend as cane yield, whereas sucrose yield showed a similar trend to cane yield. In newly planted sugarcane fields, CK₁ treatment had a significantly lower soil pH compared to all treatments (except CK₂ and I₅₀F₅₀ treatments), while F₁₀₀ treatments had significantly higher soil total nitrogen, available nitrogen and available phosphorus contents compared with CK₁ and CK₂ treatments. Compared with CK₁ treatment, I₇₅F₁₀₀ and I₁₀₀F₁₀₀ treatments significantly increased the content of soil organic carbon, labile organic carbon, particulate organic carbon, mineral associated organic carbon and microbial biomass carbon, while F₁₀₀ treatments significantly increased the carbon pool management index by 21.34%−33.18%. In terms of rhizosphere microbial diversity, CK₀ treatment showed the highest Sobs index, significantly exceeding all treatments (except I₇₅F₁₀₀ and I₁₀₀F₇₅ treatments). Over the 2 years of the study, CK₁ treatment without drip irrigation network investment had the highest net profit, but I₁₀₀F₁₀₀ and CK₂ treatments showed significantly higher yield profit growth rates than CK₁, indicating better profit growth potential. In terms of comprehensive benefit evaluation, high water-high fertilizer (I₁₀₀F₁₀₀) and medium water-high fertilizer (I₇₅F₁₀₀) treatments exhibited superior comprehensive benefits, and were identified as the most suitable drip fertigation patterns for promotion in dry sloping land of red soil in Southern China.