The problem of tapping panel dryness (TPD) that renders the rubber tree non-yielding has been in the industry for over 100 years. Many studies have been done on TPD, however, the exact mechanisms remain speculative until today, while a definitive cure for the disorder remains unavailable. Recently, a newly developed latex stimulant, RRIM HYDROBEST™ has been shown not only to increase latex production but also to reduce the TPD incidence. In order to reveal both TPD and also RRIM HYDROBEST™ mechanisms, transcriptome of latex between three groups (healthy, TPD, and TPD with RRIM HYDROBEST™) were obtained and compared. The differential expression analysis found 20, 678 and 577 statistically significant differentially expressed genes (DEGs) when comparing TPD versus Control (Comp1), TPD treated with RRIM HYDROBEST™ versus Control (Comp2), TPD with RRIM HYDROBEST™ versus TPD (Comp3), respectively. The enrichment tests retrieved a total of 119, 2,264, and 2,179 GO terms and 0, 24, and 24 pathways which might be associated with the three transcriptome profilings, Comp1, Comp2, and Comp3, respectively. Most significantly enriched KEGG pathways included alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, nitrogen metabolism, flavone and flavanol biosynthesis, and glycosaminoglycan degradation. The transcriptional responses of latex rubber tree to the TPD and RRIM HYDROBEST™ were determined and a large number of DEGs were characterised, providing important clues for further elucidation of the mechanisms of TPD stress response and RRIM HYDROBEST™ effect in rubber tree.