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Buffalo's largest employment sectors today are financial services, technology, healthcare, and education, a shift from its manufacturing-driven past. M&T Bank is headquartered downtown, while KeyBank and Bank of America maintain significant corporate operations in the city. Manufacturing has not disappeared: Ford runs a stamping plant in South Buffalo and General Motors operates its Tonawanda Engine plant along the Niagara River, keeping industrial employment part of the region's base.

Healthcare and life sciences are concentrated in the Buffalo Niagara Medical Campus, anchored by the University at Buffalo and Roswell Park Comprehensive Cancer Center, alongside health systems Kaleida Health and Catholic Health. Downtown itself is organized into distinct districts, including the Erie Canal Harbor and Waterfront, the Theatre District, and the Financial District and Government Center. The federal government also awarded the Buffalo-Rochester-Syracuse corridor $40 million to help build a semiconductor manufacturing hub along the Interstate 90 corridor.

With a medical campus drawing thousands of healthcare workers, active bank and corporate headquarters downtown, and manufacturing plants still running in South Buffalo and Tonawanda, Buffalo has steady demand for the local trades and professional services that support both institutions and neighborhoods, from commercial HVAC contractors serving hospital campuses to plumbers and electricians working the city's older housing stock.