Observations of the eco-evolutionary dynamics of genome size (GS) variation resulting and not resulting from polyploidization often discover incongruent patterns. Such varied responses likely arise because many different genomic processes contribute to changes in GS, which uniquely affect genomic and phenotypic traits, precluding a census of whether and how genome size per se effects eco-evolutionary dynamics. Regardless of the mechanism, GS scales positively with cell size and DNA content and it has been proposed that larger GS organisms have increased cellular nitrogen (N) and phosphorus (P) investments (“material costs” - arising because nucleic acids and cell membranes require N and P for synthesis) that constrain growth under nutrient limitations. Supporting this hypothesis, studies in greenhouse and field experiments show that nutrient-limiting conditions favor the fitness, growth, and abundance of diploids and smaller GS plants and nutrient-enriched conditions favor the fitness, growth, and abundance of polyploids and larger GS plants, especially under dry conditions. I argue that when organismal responses depend upon DNA content and cell size that the patterns should be equivalent regardless of the process generating GS variation. As a case in point I examine whether nutrient investment trade-offs between metabolic processes and cell synthesis are stronger for larger GS organisms by testing three integrated hypotheses: (H1) Larger GS plants have increased cellular N and P material costs resulting in more pronounced investment tradeoffs with photosynthesis (because organelles and molecules involved in photosynthesis also require N and P atoms), especially under nutrient-limiting conditions where photosynthesis rates are generally expected to be lower; (H2) Larger GS plants have larger, less responsive stomata resulting in lower instantaneous transpiration rates with GS-differences most pronounced in drier conditions (due to stomatal constraints); (H3) The complex interplay between GS, nutrients, and abiotic environmental attributes affect water-use-efficiency (WUE, photosynthesis divided by transpiration) values and eco-evolutionary dynamics. To asses these hypotheses I synthesize and compare GS, cellular nutrient investment, and primary metabolic rate data from: (1) greenhouse studies involving the autopolyploid complex, Solidago gigantea, and (2) a field survey of  >500 grasses, forbs, and legumes from eight grassland sites spanning a north-south environmental gradient in the Midwest (NutNet; https://nutnet.org), both in which nutrient amounts have been experimentally modified. Preliminary analysis of polyploid systems and plants that vary in GS independent of polyploidization show similar patterns, in that larger GS plants/cytotypes have increased cellular nutrient investments and lower rates of photosynthesis (independent of nutrients) and (instantaneous transpiration. Furthermore, WUE values were higher under nutrient enrichments and for larger GS plants. Subsequent analysis will examine how phylogenetic history and functional group influences patterns in a field context. In conclusion, these analyses provide mechanistic insight into why larger GS-plants (regardless of the process generation variation) tend to show more positive growth responses to nutrient enrichments – they have increased cellular nutrient requirements but less access to resources through lower transpiration rates, potentially leading to ecological costs (less competitive due to lower photosynthesis rates) and/or benefits (increased WUE) where the selective implications depend upon environmental context.