Background: Heat-related illnesses (HRIs) are a significant public health concern, particularly in regions experiencing extreme temperatures. This observational study aims to evaluate the clinical, hematological, and biochemical spectrum of HRIs and identify prognostic markers, providing insights into mitigating their impact in Northwestern India. Methods: We conducted a hospital-based observational study involving 23 patients diagnosed with HRIs at Sawai Man Singh (SMS) Hospital, Jaipur, from May 31 to June 30, 2024. Adults over 18 years with clinical, hematological, and biochemical diagnoses of HRIs were included, while those with hyperthermia due to infections or drug use were excluded. Data were collected using a prestructured proforma that covered a comprehensive history, physical examination, and relevant investigations. Statistical analysis was performed using SPSS v20 and GraphPad Prism v5, with significant correlations determined through odds ratios (OR) and multiple logistic regression analysis. Results: The study cohort consisted of 23 patients, with a mean age of 54.6 years; males comprised 74% of the population. Fever was a universal symptom, and 96% (22/23) presented with altered sensorium. Key clinical and laboratory findings included leukocytosis (60%), elevated levels of aspartate aminotransferase (AST, 100%) and alanine aminotransferase (ALT, 78%), hyponatremia (74%), hypokalemia (45%), lactic acidosis (65%), and acute kidney injury (52%). Mortality was observed in 56.5% of patients, with significant associations found between mortality and leukocytosis (OR 3.5, p = 0.043) and elevated ALT levels (OR 5.2, p = 0.007). No significant correlation was noted between mortality and acute kidney injury or electrolyte disturbances. Multivariate analysis identified the need for mechanical ventilation as an independent predictor of mortality [OR: 12.45, 95% confidence intervals (CI): 1.02–152.62, p = 0.048], highlighting the severity of respiratory complications in heat stroke. Conclusion: This study identifies key clinical, hematological, and biochemical parameters associated with HRIs and highlights the need for targeted interventions to improve patient outcomes. The identification of prognostic markers such as leukocytosis and elevated ALT levels can guide clinical management and preventive strategies. Future research should focus on developing comprehensive prevention programs and exploring therapeutic advancements to reduce the burden of HRIs in vulnerable populations.