Tobacco is an agricultural commodity with great economic significance. Producers recognize that the flavor characteristics of filler tobacco clear-out (FTLs) affect the quality of cigar tobacco items. To identify the major volatile organic compounds (VOCs) responsible for differences in FTLs, E-nose, HS-SPME-GC–MS, and HS-GC-IMS were employed for multi-dimensional analysis of nine groups of FTLs at various fermentation stages. The E-nose results indicated a progressive increase in nitrogen-oxygen compounds during fermentation. Coupled with these findings, HS-SPME-GC–MS identified 56 VOCs, and HS-GC-IMS revealed 55 VOCs in the FTLs. Principal component analysis (PCA) suggested that FTLs from various fermentation stages of the Yunxue No 39 tobacco plant exhibit significant differences. Partial least squares discriminant analysis (PLS-DA), along with the variable importance in projection (VIP) method for feature selection, pinpointed 12 VOCs as the essential unmistakable metabolites embroiled within the agrarian fermenting prepare of matured FTLs. During the fermentation process, these crucial metabolites are predominantly enriched in pathways including pyruvate metabolism, phenylalanine metabolism, as well as nicotinate and nicotinamide metabolism. The study provides insights into the differences and diversity of FTLs at agricultural fermentation stages. It offers valuable information for optimizing the quality of agricultural fermentation and guiding the directional fermentation of tobacco leaves.