The climate warming trend challenges the chemical risk associated with wine production worldwide. The present study investigated the possible difference between chemical wine profile during the drought year 2012 compared to the post-drought year 2013. Toxic metals (Cd and Pb), microelements (Mn, Ni, Zn, Al, Ba, and Cu), macroelements (Na, Mg, K, Ca, and P), isotopic ratios (87Sr/86Sr and 206Pb/207Pb), stable isotopes (δ18O, δ13C, (D/H)I, and (D/H)II), and climatic data were analyzed. The multivariate technique, correlation analysis, factor analysis, partial least squares-discriminant analysis, and hierarchical cluster analysis were used for data interpretation. The maximum temperature had a maximum difference when comparing data year apart. Indeed, extreme droughts were noted in only the spring and early summer of 2012 and in 2013, which increased the mean value of ground frost days. The microelements, macroelements, and Pb presented extreme effects in 2012, emphasizing more variability in terms of the type of wine. Extremely high Cd values were found in the wine samples analyzed, at up to 10.1 µg/L. The relationship between precipitation and δ18O from wine was complex, indicating grape formation under the systematic influence of the current year precipitation, and differences between years were noted. δ13C had disentangled values, with no differentiation between years, and when coupled with the deuterium-hydrogen ratio, it could sustain the hypothesis of possible adulteration. In the current analysis, the 87Sr/86Sr showed higher values than in other Romanian studies. The temperature had a strong positive correlation with Pb, while the ground frost day frequency correlated with both Pb and Cd toxic elements in the wine. Other significant relationships were disclosed between the chemical properties of wine and climate data. The multivariate statistical analysis indicated that heat stress had significant importance in the chemical profile of the wine, and the ground frost exceeded the influence of water stress, especially in Transylvania.