On course to maximization and optimization of a two-phase closed thermosyphon, this paper expounds on multiple impactful factors in an experimental and numerical setting. Among various fluids, 1-Butanol with 6% concentration, due to having the largest difference in surface tension with water, engendered the most favorable outcome. Response Surface Method has been employed to develop two correlations for efficiency and the thermal resistance of the thermosyphon paving the way for more accurate quantifications without necessarily running costly experiments. Other studied factors based on heat transfer coefficients of evaporator and condenser have been analyzed. The resultant numbers suggest an increase up to roughly 40% and 9% by changing power input and fluid, respectively. Also, enhancements falling within the range of 16 to 20% with the employment of 6% water-Butanol were observed by manipulation of filling ratio. However, coolant mass flow rate influence was limited to less than 10% when exposed to a 40% jump in flow rate if the working fluid was the same, implying its poor dominance in thermal performance of thermosyphon. As 1-Butanol proved superior among enhancing determinants, two numerical cases based on this factor were analyzed, confirming experimental findings while concurrently revealing distinctive phase-change patterns arising from the self-rewetting fluid. •Effect of different self–rewetting fluids on TPCT performance has been investigated.•The 1-Butanol, 1-Pentanol, and 1-Hexanol have been selected as self–rewetting fluids.•Effect of heat input, FR and coolant flow rate on TPCT performance have been studied.•Water/1-Butanol 6% has augmented the he by 8.6% at 250 W comparing with pure water.•Numerical simulation has been done for water and Water/1-Butanol 6% charged TPCT.