Background: Viticulture bioclimatic indexes like the Heliothermal Index (HI), Cool Night Index (CI), and Dryness Index (DI), can be used to assess the influence of climate on grapes’ quality. Methods: HI, CI, and DI + total seasonal irrigation were utilized to assess the effect of climate on the flavonoids content and composition of two Vitis vinifera seedless varieties, ‘Summer Royal’ and ‘Crimson Seedless’, both grown in Apulia (Southern Italy). Results: The flavonoids content was significantly affected by variety and climate conditions on the base of HI, CI, and DI + total seasonal irrigation. Factor analysis applied to climate indexes and flavonoids showed that anthocyanins and flavonols were negatively and positively correlated to CI in both varieties, respectively. Additionally, warmer night temperatures determined higher fla-van-3-ols. HI increase promoted anthocyanins, flavonols, and flavan-3-ols content in Crimson Seedless, whilst it induced an opposite trend in Summer Royal. Finally, DI + total seasonal irrigation showed to be positively linked to flavonols content and negatively linked to anthocyanins content just in the case of Crimson Seedless. Significant regression models were also determined between climate indexes and productive parameters (i.e., yield, TSS, TA, pH, bunch, and berry weight). Conclusions: Climate indexes HI, CI, and DI + total seasonal irrigation showed an effect on quality grape parameters like flavonoids and contributed to building predictive models when new climatic zones are going to be evaluated for the production of table grapes.