Properly quantifying environmental heat stress (HS) is still a major challenge in livestock breeding programs, especially as adverse climatic events become more common. The definition of critical periods and climatic variables to be used as the environmental gradient is a key step for genetically evaluating heat tolerance (HTol). Therefore, the main objectives of this study were to define the best critical periods and environmental variables (ENV) to evaluate HT and estimate variance components for HT in Large White pigs. The traits included in this study were ultrasound backfat thickness (BFT), ultrasound muscle depth (MDP), piglet weaning weight (WW), off-test weight (OTW), interval between farrowing (IBF), total number of piglets born (TNB), number of piglets born alive (NBA), number of piglets born dead (NBD), number of piglets weaned (WN), and weaning to estrus interval (IWE). Seven climatic variables based on public weather station data were compared based on three criteria, including the following: (1) strongest G×E estimate as measured by the slope term, (2) ENV yielding the highest theoretical accuracy of the genomic estimated breeding values (GEBV), and (3) variable yielding the highest distribution of GEBV per ENV. Relative humidity (for BFT, MDP, NBD, WN, and WW) and maximum temperature (for OTW, TNB, NBA, IBF, and IWE) are the recommended ENV based on the analyzed criteria. The acute HS (average of 30 days before the measurement date) is the critical period recommended for OTW, BFT, and MDP in the studied population. For WN, WW, IBF, and IWE, a period ranging from 34 days prior to farrowing up to weaning is recommended. For TNB, NBA, and NBD, the critical period from 20 days prior to breeding up to 30 days into gestation is recommended. The genetic correlation values indicate that the traits were largely (WN, WW, IBF, and IWE), moderately (OTW, TNB, and NBA), or weakly (MDP, BFT, and NBD) affected by G×E interactions. This study provides relevant recommendations of critical periods and climatic gradients for several traits in order to evaluate HS in Large White pigs. These observations demonstrate that HT in Large White pigs is heritable, and genetic progress can be achieved through genetic and genomic selection.