Oromucosal delivery of olanzapine (OLZ) is an optimal strategy to overcome low oral bioavailability as well as improve medication adherence. However, its poor aqueous solubility may hinder its absorption through the buccal mucosa. The aim of the study is to enhance OLZ solubility and dissolution via cocrystal formation, followed by incorporation into an orodispersible tablet (ODT) based on an effervescent mixture and crospovidone as a superdisintegrant mixture. OLZ was cocrystallized with different carboxylic acids using slow solvent evaporation, and the optimal cocrystal formula was subjected to solid state characterization. Central composite design (CCD) was used in the modeling and optimization of the ODT independent variables (amounts of crospovidone and effervescent mixture). The optimized OLZ cocrystal ODTs were subjected to microenvironmental pH, stability, and in-vivo studies. The results revealed that the OLZ:itaconic acid at 1:1 molar ratio showed a 7.86 fold increase in OLZ solubility and 86.71±1.07% dissolution efficiency (DE60%) with FTIR, XRPD, and DSC diffractograms that confirmed the cocrystal formation. The optimized OLZ cocrystal ODTs exhibited hardness of 3.6 ± 0.1 kg/cm2, disintegration time of 11.66 ± 1.52 sec, wetting time of 36.33 ± 2.51 sec, and 94.26 ± 2.77 % OLZ released within 15 min with a DE60 % of 91.65 ± 0.98 %. Finally, the optimized OLZ cocrystal ODTs showed a significant (p < 0.01) higher Cmax and AUC with a relative bioavailability of 139.08% compared to the Schisolazine©10mg ODTs. These results suggest that OLZ:itaconic acid cocrystal incorporated into an ODT containing a superdisintegrant mixture of effervescence mixture and crospovidone is a potential approach for enhancement of oromucosal delivery of OLZ.