Under climate-change, micro-irrigation practices like sub-surface drip-irrigation (SSDI) coupled with optimizedfertigation and foliar-nutrition, may improve crop-productivity and quality. Hence, current study in cotton (Gossypium hirsutum L.) comprised of three SSDI-regimes [60, 80, 100% ETc], two N-fertigation levels [80, 100% RDN] and two nutrient-application methods [foliar-spray of KNO3 & MgSO4 (Mfoliar) versus fertigation (Mfert)] in factorial randomized-complete-block-design besides three additional controls (surface-drip + N100 + Mfoliar; surface-drip + N100 + Mfert; flood-irrigation + soil RDN + Mfoliar). The results indicated that SSDI at 80%ETc enhanced seed-cotton-yield by 5.3 and 9.9 %, ginning out-turn (GOT) by 2.1 and 4.8 %, fiber-length by 5.7 and 7.6%, lint-index by 5.8 and 11 % and protein-yield by 7.8 and 11.6%, over 60%ETc in 2019 and 2020. Oil-content, oil-yield, cake-content, and cake-yield varied significantly with increased irrigation from 60 to 100% ETc, underscoring the importance of adequate water for oil-synthesis in cottonseeds. Fatty-acid composition was sensitive to irrigation-levels, with significant reduction in saturated-fatty-acid (SFA) and unsaturated-fatty-acid (UFA) by 5.4 and 5.5 %, and monounsaturated-fatty-acid (MUFA) and polyunsaturated-fatty-acid (PUFA) by 2.9 and 5.9 % at 60%ETc over 80%ETc during 2019 and 2020, respectively. Polyunsaturated:saturated (P/S) index, vital for human cardio-vascular health, increased by 5.2 and 7.1 % under 60%ETc. To harness higher yield with better quality fiber, protein, oil-yield and cottonseed-cake, SSDI at 80%ETc proved optimal, with noadditional benefits beyond this level. Enhancing fertigation from 80 to 100%RDN slightly enhanced UFAs and reduced SFAs. Higher UFAs is desirable for reducing low-density lipoprotein (LDL) cholesterol-levels. Foliarspray of KNO3 & MgSO4 enhanced GOT, lint-index, UFAs, MUFA:PUFA and P/S index over fertigation. SSDI improved both fiber and seed-composition over flooding. Overall, SSDI at 80%ETc, combined with fertigation at 80%RDN and foliar-fertilization offers substantial benefits for cotton-productivity and quality in water-scarce agro-ecologies. These practices improve water-use-efficiency and sustainability, hence, enhancing resilience and economic-viability of cotton-industry amidst environmental-challenges.