In 1999, COSI was moved to a 30000 m2 (320000 sq ft) facility, designed by Japanese architect Arata Isozaki along a bend in the Scioto River in the Franklinton neighborhood.

[1] Until the COVID-19 pandemic, COSI operated the largest outreach education program of any science museum in the United States.

[5] Upon relocating in 1999, COSI was developed with large, self-contained, themed atria, each dedicated to a single topic and designed as immersive theatrical learning worlds.

As of 2018, COSI contains seven main exhibit areas: Ocean, Energy Explorers, Space, Progress, Gadgets, Life, and the American Museum of National History Dinosaur Gallery.

Accessed via an underwater cave through a crashed shipwreck, the cavern path splits as guests pass to the right or left.

The pathway to the right leads to a docked submarine laboratory where hands-on exhibits explore the realities of ocean research, submersibles, SCUBA, water pressure, and remote-operated vehicles.

Space was originally located on Level 2 in its own enclosed atrium exhibit area, entered via a "black hole" spinning funhouse hallway meant to disorient guests.

However, Space remains the only one of COSI's seven learning worlds to not have its own dedicated, theatrical, immersive atrium, instead being located on the bright Mezzanine bridge.

After visitors walk through Progress in 1898, they turn the corner and enter the same intersection of the same town 64 years later in 1962, where a new set of hopes and fears have arisen.

The Gadgets exhibit area contains many classic science museum hands-on experiments, such as pulleys, wind tunnels, plasmaglobes, magnets, light bulbs, engines, and counterweights.

A take-apart menu allows visitors to disassemble donated phones, computers, clocks, and other electronic devices, which are recycled afterward.

retail store, and five meeting rooms utilizing refurbished areas within the former Central High School, which the new COSI location was built around.

[9] The museum is designed to appear progressively futuristic from the neighborhood of Franklinton, while from downtown Columbus it uses the exterior of the original Central High School to blend into the city.

With an initial construction budget of over $210 million, high maintenance costs of the new facility, "six-figure" utility bills, and "lower-than-expected" ticket sales, COSI's reliance on admission revenue proved an unsuitable long term plan.

[10] In 2004, the museum spearheaded an effort to assess a property tax levy, chaired by former NASA astronaut John Glenn.

The levy would have imposed a property tax on residents of Franklin County, who would receive free admission in return.

[11] Two of the original exhibit areas were closed permanently (called i|o and SimZone, the spaces they formerly occupied are now Gallery 1 and Energy Explorers, respectively).

Closures from 2004 that have since been reversed include Space (relocated to Level 1 in 2005, then to the Mezzanine in 2012), the original Gallery 1 (space reused as WOSU@COSI in September 2006[12]), Adventure (re-opened as an additional-charge experience in September 2010[13]), CityView (still off-limits to the public; now available for special events), and the Planetarium (re-opened in November 2014 as the final piece of the building to come back online[14]).

The museum has hosted EINSTEIN, An Exhibition on the Man and his Science (2007), Gregor Mendel: Planting the Seeds of Genetics (2007), CSI: The Experience (2008), Geckos: From Tail to Toepads (2011), Dinosaurs: Explore.