We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy squashy polymeric nanovehicles were fabricated by tailored co-assembly of amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-Cysteamine (TAT)-linked MEL. Thanks to asymmetric alkyl chain configuration of MEL, the polymeric nanovehicles show structural flexibility as well as deformability, which can be confirmed by XRD, DSC, and NMR analyses. Those properties enable the vehicle to pass through between intercellular lipids in the stratum corneum. Moreover, co-assembly of TAT-linked MEL with the squashy nanovehicles significantly enhanced cellular uptake. From the in vivo skin penetration test revealed that our CPP-patchy squashy nanovehicles remarkably improved transdermal delivery efficiency.