Myasishchev was tasked with building an intercontinental jet-powered bomber, something veteran aircraft designer Tupolev said was impossible. Myasishchev managed to complete the first prototype 103M (called M-4 Bear in the West) bomber ten months after go-ahead. Myasishchev would later play a key role in Soviet spaceplane development.

In 1951 to 1953 Korolev's design bureau had prepared an experimental trisonic ramjet design, the EKR.The expert commission ifelt that there were still many technical problems to be solved, most of which were better handled by an aircraft designer rather than Korolev. Further, Korolev had to place the highest priority on development of the R-7 ICBM. Therefore a final government decree on 20 May 1954 authorised the Lavochkin and Myasishchev aircraft design bureaux to proceed in parallel with full-scale development of trisonic intercontinental cruise missiles.

Council of Soviet Ministers (SM) Decree 957-409 'On transfer of intercontinental cruise missile work to the Ministry of Aviation Industry' was issued. Korolev had to place the highest priority on development of the R-7 ICBM. Therefore the final government decree authorised the Lavochkin and Myasishchev aircraft design bureaux to proceed in parallel with full-scale development of trisonic intercontinental cruise missiles. Both missiles would use ramjet engines by Bondaryuk, astronavigation systems by R Chachikyan, inertial navigation systems by G Tolstoysov, and aerodynamics developed by TsAGI (Central Hydrodynamics Institute). Lavochkin's Burya would use rocket booster engines built by Glushko, while Myasishchev's Buran would use Isayev engines. Both missiles were to deliver a nuclear warhead over an 8,500 km range. But the warhead design specified for the Lavochkin missile had a total mass of 2,100 kg, while that for the Myasishchev missile weighed 3,500 kg.

Council of Soviet Ministers (SM) Decree 'On termination of work on the 40 Buran intercontinental cruise missile' was issued. Buran was being prepared for its first flight when Myasishchev's project was cancelled. After successful flight tests of Lavochkin's Burya missile, the Soviet leadership did not see any need for continued development of a parallel ramjet design. Following the cancellation, Myasishchev sought approval for test of an air-launched version.

On the basis of the immense delta-winged M-50 bomber Myasishchev proposed the RSS-52 aerospace vehicle. The M-50 derivative would enter a circuit 1,000 km from base, accelerate to supersonic speed, and then launch the M-44. The M-44 would accelerate to hypersonic velocity, conduct a high speed run of an overwater circuit, and then splash down in the sea. In the United States, the X-15 was being developed to answer analogous questions. However due to the expense and technical problems, Myasishchev was unable to convince the leadership to approve the RSS-52.