A newly formulated water-based ethephon namely RRIM HYDROBEST™ has been developed by Malaysian Rubber Board with the objective of producing an improved latex stimulant for rubber tree (Hevea brasiliensis) than the currently available formulations in the market. Main aim of introducing the new product is to overcome high incidence of tapping panel dryness (TPD), which eventually cause low latex production. Field trial on RRIM 3001 clones showed that the application of RRIM HYDROBEST™ resulted in the highest land productivity with 1905 kg/ha/year and lower TPD incidence with only 30.8% compared to non-simulated and other types of stimulated trees (Ethephon and Mortex). However, the sucrose content in latex, which is an important carbon source for natural rubber, was similar in all types of latex stimulant-applied trees. Other commercial rubber clones grown in Malaysia such as PB 260, PB 350, RRIM 928, RRIM 929 and RRIM 2001 also have similar responses to RRIM HYDROBEST™ with low TPD incidence especially the partial dryness incidence compared to the non-simulated rubber trees. Based on transcriptome analysis, the latex stimulation mechanism by RRIM HYDROBEST™ is very complex, where 77 transcription factors with mostly from ERF family were differentially expressed. Most of the genes and pathways identified through this analysis were related to oxidative stress and enhanced nitrogen metabolism, which could be vital to counter excessive reactive oxygen species (ROS) in the TPD-affected rubber trees. The knowledge from this study is crucial for not only understanding the way latex stimulant and TPD work but also providing a platform for creating super formulation of latex stimulant.