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Abstract We present an extensive archival analysis of a sample of local galaxies, combining multiwavelength data from GALEX, Spitzer, and Herschel to investigate “blue-side” mid-infrared (MIR) and “red-side” far-infrared (FIR) color–color correlations within the observed infrared spectral energy distributions. Our sample largely consists of the KINGFISH galaxies, with the important addition of a select few including NGC 5236 (M83) and NGC 4449. With data from the far-ultraviolet (∼0.15μm) through 500μm convolved to common angular resolution, we measure the photometry of kiloparsec-scale star-forming regions 36″ × 36″ in size. Star formation rates (SFRs), stellar masses, and metallicity distributions are derived throughout our sample. Focusing on thef₇₀/f₅₀₀“FIR” andf₈/f₂₄“MIR” flux density ratios (colors), we find that a subsample of galaxies demonstrate a strong IR color–color correlation within their star-forming regions, while others demonstrate uncorrelated colors. This division is driven by two main effects: (1) the local strength of star formation (SF) and (2) the metal content of the interstellar medium (ISM). Galaxies uniformly dominated by high surface densities of SF (e.g., NGC 5236) demonstrate strong IR color–color correlations, while galaxies that exhibit lower levels of SF and mixed environments (e.g., NGC 5457) demonstrate weaker or no correlation—explained by the increasing effect of varying ISM heating and metal content on the IR colors, specifically in the MIR. We find large dispersion in the SFR–L₈(8μm luminosity) relation that is traced by the metallicity distributions, consistent with extant studies, highlighting its problematic use as an SFR indicator across diverse systems/samples.