Cheese is one of the most consumed fermented animal-based products globally, rendering its quality assessment and evaluation of substantial economic interest. Understanding the degree of cheese homogeneity is paramount for designing effective sampling strategies, yet this information is largely lacking. This study investigates the homogeneity of a cheese wheel based on the distribution of volatile compounds, microbiota, sodium chloride content, and pH, combined with sensory analyses. The outer zones of the cheese wheel were primarily characterized by the presence of sulfur compounds, esters, pyrazines, ketones, Streptococcus thermophilus, high sodium chloride concentration and high pH. In contrast, the inner zones of the cheese wheel were dominated by lactones, carboxylic acids, aldehydes, Lactobacillus delbrueckii subsp. lactis and Lacticaseibacillus paracasei. The presence of alcohols and Lactobacillus helveticus was observed throughout the cheese wheel. Furthermore, sensory descriptions were found to match predominantly with the aroma of the volatile compounds identified. The cheese wheel was found to be heterogeneous in all investigated characteristics. Our results indicate that the level of cheese homogeneity should be considered when designing sampling strategies, as these significantly impact the accuracy and reproducibility of analytical outcomes.