The majority of eukaryotic protein-coding genes contain low complexity regions (LCRs), which serve as a distinct source of adaptive variation, functional diversification, and evolutionary novelty. The intricate governance of low complexity regions (LCRs) involves the interplay of selection and mutation dynamics, necessitating a more comprehensive understanding of their complex interdependence. Our investigation demonstrates that positively-selected sites (PSS) and low complexity regions (LCRs) are predominantly located in terminal gene regions across most Tetrapoda clades. In seven of the twelve clades studied, PSS are notably favored within LCRs, revealing a positional specificity for PSS within genes. Central-PSS genes are mainly associated with defense responses, while terminal-PSS genes serve non-specific functions. Furthermore, genes with LCRs in the Tetrapoda clade exhibit a higher %GC and lower ω (dN/dS) compared to those without LCRs, indicating intense purifying selection despite rapid functional diversity. Our findings highlight a consistent prevalence of LCRs at lower purity levels, with a clear preference for specific gene positions as LCR stretch purity increases, suggesting a composition-dependent evolutionary role. Overall, these results significantly contribute to our understanding of how the intricate interplay between selection and LCRs shapes genetic diversity and adaptation within the Tetrapoda clade.