This paper outlines the effect of farming systems with reference to season on the body condition score (BCS) and adaptive profile (physiological, hemato-biochemical, hormonal, enzymatic and reproductive parameters) of Nellore sheep. In trial 1, sixty ewe-lambs were allotted to extensive, semi-intensive, and intensive rearing systems (n = 20) and evaluated for BCS at puberty, mating, 2 weeks pre-lambing and 2, 4, 8, and 12 weeks post-lambing. In trial 2, eighteen rams were distributed evenly to three farming systems (n = 6) and evaluated for physiological, hemato-biochemical, hormonal, enzymatic, and reproductive parameters concerning three seasons. Although the scores did not differ among the groups, the Kruskal-Wallis ranks of BCS revealed a higher energy status of intensive ewes at different physiological conditions. The sheep reared under extensive and semi-intensive systems displayed higher temperature, pulse rate and respiratory rate with predominant effects in summer season. Similarly, both systems exhibited higher WBC and lower haemoglobin, PCV, and RBC contents without affecting MVC, MCH, MCHC, and differential leucocyte count. The percent haemoglobin and RBC count were higher in winter compared to summer months, whereas WBC count followed an exactly opposite pattern. The sheep reared in intensive system showed higher glucose, total protein, albumin, cholesterol, T3, T4, calcium, and phosphorus; however, the globulin, creatinine, uric acid, aspartate amino transferase (AST), alanine amino transferase (ALT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase, and catalase levels were elevated in extensive and semi-intensive systems. The dartos muscle extension (DME) and scrotum sweating rate (SSR) were higher for the sheep reared under extensive system, especially during summer season; while the seminal parameters viz., total sperm count, progressive sperm motility, and plasma membrane integrity were lower for extensive and semi-intensive sheep. No interactions were noticed for any of the parameters, except for cortisol, DME, and SSR, which showed significant interactions for rearing system vs. season. Our results showed dynamic adaptive mechanisms of the Nellore sheep in relation to different stressors like grazing for long distances, inadequate nutrition, and heat stress, revealing the heat resilient ability in harsh environmental conditions. Further, the analyzed vector plot showed that the AST, GPx, Cortisol, SOD, Catalase, WBC, PR, T4, total abnormalities, and major abnormalities were the major contributors for adapting during combined stressors.