The manufacturing of parts from nickel-based superalloy, such as Inconel-800 alloy, represents a challenging task for industrial sites. Their performances can be enhanced by using a smart cutting fluid approach considered a sustainable alternative. Further, to innovate the cooling strategy, the researchers proposed an improved strategy based on the minimum quantity lubrication (MQL). It has an advantage over flood cooling because it allows better control of its parameters (i.e., compressed air, cutting fluid). In this study, the machinability of superalloy Inconel-800 has been investigated by performing different turning tests under MQL conditions, where no previous data are available. To reduce the numerous numbers of tests, a target objective was applied. This was used in combination with the response surface methodology (RSM) while assuming the cutting force input (F_c), potential of tool wear (VB_max), surface roughness (Ra), and the length of tool–chip contact (L) as responses. Thereafter, the analysis of variance (ANOVA) strategy was embedded to detect the significance of the proposed model and to understand the influence of each process parameter. To optimize other input parameters (i.e., cutting speed of machining, feed rate, and the side cutting edge angle (cutting tool angle)), two advanced optimization algorithms were introduced (i.e., particle swarm optimization (PSO) along with the teaching learning-based optimization (TLBO) approach). Both algorithms proved to be highly effective for predicting the machining responses, with the PSO being concluded as the best amongst the two. Also, a comparison amongst the cooling methods was made, and MQL was found to be a better cooling technique when compared to the dry and the flood cooling.