In this study, we applied a systematic approach to establish an iterative workflow and to drive the chemical design of thermosensitive, in situ forming injectables as a function of the intended target product profile. Self-assembly, mechanical properties, physical state, and thermal transition behavior were assessed via nuclear magnetic resonance, oscillatory rheology, turbidimetry and visual inspection techniques. Thus, poly(N-isopropylacrylamide) (PNIPAM) and poly(2-alkyl-2-oxazoline)s (PAOx)s with LCSTs below body temperature were studied before and after grafting them onto azido-substituted hyaluronic acid (HA) via strain-promoted azide-alkyne cycloaddition (SPAAC). Ultimately, we identified critical material attributes able to guide the pharmaceutical development of in situ gelling thermosensitive polymers.