Megacities are a great source of urban aerosol particles, which can impact cloud formation and the local hydrological cycle. However, the aerosol-cloud interaction in megacities, especially in their different microclimates, is poorly understood. In the present study, the physicochemical and biological properties of urban particles, along with their ice-nucleation abilities as a function of size (1.0 μm to 10 μm), were simultaneously characterized at two sites across the Mexico City Metropolitan Area (MCMA). We found apparent differences in the chemical composition, criteria pollutants, and biological content between northern and southern sites in the MCMA. The urban MCMA aerosol particles were found to act as ice-nucleating particles (INPs), with average concentrations ranging between (0.04 ± 0.04) L^-1 (at -15 °C) and (23 ± 17) L^-1 (at -30 °C). The southern MCMA samples were found to be more efficient INPs, and their ice nucleation abilities correlated positively with PM_2.5, potassium, and sulfur. On the other hand, the ice nucleation abilities of the measured urban particles at both sites did not correlate with their size nor the presence of biological particles. Overall, the aerosol physicochemical and biological compositions, their sources, and their role in cloud formation at both sites were found to be different. Therefore, the present results demonstrated the presence of two different microclimates within the MCMA. This highlights the importance to consider that aerosol-cloud interactions within a megacity may vary widely, especially when assessing the role of INPs in the development of extreme precipitation events.