In 2015, California established a mandate that requires on-road greenhouse gas (GHG) emissions be reduced by 40 percent below 1990 levels by 2030. We explore the feasibility of meeting this goal by large-scale commercialization of drop-in biofuels. Drop-in biofuels, although not clearly defined, are a class of fuels that can be produced from biomass and blended with either crude oil or finished fuels without requiring equipment retrofits. This article focuses on thermochemical routes at or near commercialization. We provide a bottom-up, spatially-explicit cost analysis to evaluate whether California can meet its 2030 GHG reduction target with drop-in fuels alone. A takeaway from our analysis is that drop-in fuels, if their performance is consistent with small-scale and simulated results, can be viable low-carbon substitutes for gasoline and diesel. We find that California can meet, and even exceed, its 2030 GHG emissions target for on-road vehicles with drop-in biofuels alone, but this requires use of biomass resources located outside the state. To meet the 40% reduction target in a cost-effective manner, pyrolysis of herbaceous agricultural residues (96% of total fuel output) and the conversion of woody residues via methanol-to-gasoline (4%). This scale of production would require 58 mmt of biomass feedstock, or 20% of total available biomass residues in the US. For comparison, California is responsible for 11% of transportation-related petroleum consumption in the U.S. The approximately 5 billion gallons (19 billion liters) per year of drop-in fuel would displace 30% of gasoline and 60% of diesel demand in California. If electricity offset credits are eliminated, the target can be met with a similar scale of production, but methanol-to-gasoline becomes the dominant process (>99%), biomass requirements increase by 33%, and average production costs increase by 20%. Following this policy pathway would increase national biofuel production by 30% relative to 2015 production levels.