In Atomic force microscopy (AFM), the tip-sample interaction force can be measured through two primary detection techniques: optical beam detection (OBD) and electrical (self-sensing) readout. Compared to the optical method, the convenience of the self-sensing readout AFM measurements comes at the cost of higher force noise. In the self-sensing method, there is a trade-off between reducing the force noise and maintaining the cantilever characteristics (e.g. resonance frequency, spring constant, quality factor, and planar dimension) within the practical limits. The core of my research was the development of hybrid multilayer self-sensing cantilevers with up to one order-of-magnitude better force sensitivity than state-of-the-art silicon self-sensing cantilevers. Thanks to a material engineering approach combined with non-standard fabrication methods, the developed cantilevers are designed such that a polymer core is sandwiched between two hard thin films. The multilayer self-sensing cantilevers are designed to be thick and soft, thus combining increased deflection sensitivity with low spring constants, and hence increasing the force sensitivity. The high force sensitivity of the hybrid multilayer cantilevers is accompanied by a high detection bandwidth in AC modes. This originates from having a viscoelastic material as the main structural layer, which causes low quality factor and hence high tracking bandwidth. In terms of the imaging speed, the multilayer cantilevers show four times faster response compared to their silicon counterparts. In addition, the hermetically sealed self-sensing multilayer cantilevers can be deployed for various scanning probe microscopy (SPM) applications in liquid as well as in air and vacuum with additional coatings. For even further increase of the deflection sensitivity, newly developed high-gauge factor strain sensors can be incorporated to the multilayer cantilevers governed by their adaptable process flow. As a proof of concept, I show that atomically thin MoS2 piezoresistors can be incorporated into SU8 cantilevers. However, the MoS2 piezoresistors have very high resistance, which has an adverse effect on the force noise of the cantilevers. One common strategy to alleviate this high resistance is doping the MoS2 piezoresistors. In this work, I show that SU8 can act as a structural cantilever layer as well as an n-type doping source and an encapsulation solution for the MoS2 piezoresistors. In addition to the force resolution and the tracking ability, the quality and the repeatability of any AFM image is also correlated with the cantilever tip shape (sharpness) and durability. SU8 cantilevers have shown very good tracking ability but polymers are subjected to high wear-rate as a tip material. In the scope of my research, I have also developed fabrication recipes to integrate sharp, low wear-rate, silicon nitride tips into the pure SU8 cantilevers as well as the polymer-core multilayer cantilevers. Furthermore, to extend the ease of use and versatility of AFM, a closed-loop scanner based on a sidewall piezoresistive displacement sensor is presented. Such a closed loop scheme compensates the piezotube scanner nonlinearities, namely hysteresis and creep. This closed-loop system reshapes the piezotube drive signal through our developed FPGA-based Proportional-Integral (PI) controller.