Although breast cancer mortality rates have declined, effective localized delivery systems to reduce post-surgical recurrence remains challenging. We developed an injectable in situ forming hybrid hydrogel incorporating liposomal combretastatin A4 (CA4) and plasmid green fluorescent protein (pGFP) lipoplexes for prolonged simultaneous drug and gene delivery to the tumor microenvironment. Cationic liposomes were synthesized using cholesterol/DOTAP2 (1:1 M ratio) and complexed with pGFP as the reporter gene. CA4 loaded liposomes made of HSPC3/DSPE4/DPPG5/Cholesterol/CA4 (molar ratios: 5/20/5/15/55) were synthesized with 84 % encapsulation efficiency. The hydrogel was injectable at room temperature, gelling after 30 min at 37 °C, with 18.38 % swelling index and 14.21 % degradation rate over 30 days. Drug release studies showed 32.22 % CA4 release over 21 days. In vivo studies in BALB/c mice demonstrated significant tumor growth reduction in the treatment group. Histopathological studies revealed that the administration of the hybrid hydrogel induced the highest tumor necrosis with no severe damage to other organs. Notably, animal imaging studies indicated prolonged and enhanced gene expression, surpassing that of the PEI 25 kDa standard. These findings underscore the hybrid hydrogel as a potent delivery platform, facilitating localized simultaneous drug and gene delivery, enhancing anti-angiogenic effects, sustained gene expression and ensuring formulation stability for extended therapeutic benefits.