Two-dimensional (2D) metal carbides, nitrides, and carbo nitrides (MXenes) are considered potent alternatives to carbon-based 2D materials for inkjet printing. On the other hand, the low oxidation resistance and vulnerability to restacking issues make developing novel MXene-based materials with 3D structures essential. Herein, we developed highly stable aqueous inks consisting of Nitrogen and Sulphur-codoped (V2C MXene nanoflower (Nf)/holey multiwalled carbon nanotube (h-MWCNT)) hybrids. The V2C MXene Nf architectures with an average particle size of 284.6 ± 78.8 nm were synthesized using a facile ultrasonic treatment followed by a freeze-drying process without any template. The 3D V2C MXene architectures were mixed with holey MWCNTs to enhance the oxidation stability of MXene. Furthermore, creating holes in the MWCNT structure enhanced the printability of the inks and boosted the electrochemical performance of the printed sensors significantly compared to pristine MWCNT-based hybrids. The inks were inkjet printed on flexible substrates to fabricate electrochemical sensors. The electrocatalytic activity of the printed sensors was assessed against nicotine. The results indicated that our novel printed sensor design performed much better than already reported sensors in terms of linear range (10–500 µM) and LOD (0.058 µM).